Sự tương tác giữa exosome và autophagy trong chấn thương tủy sống: mục tiêu tích cực mới cho ứng dụng điều trị

Springer Science and Business Media LLC - Tập 391 Số 1 - Trang 1-17 - 2023
Ruiyu Li1, Qi Hu2, Shengyuan Xu2, Zhenyu Luo2, Dong-hua Shao2
1Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, Anhui Province, China
2Jiangsu University, Zhenjiang, 212001, Jiangsu Province, China

Tóm tắt

Tóm tắtChấn thương tủy sống (SCI) là một căn bệnh chấn thương lâm sàng rất nghiêm trọng với tỷ lệ tàn tật cao. Nó không chỉ gây ra chứng rối loạn chức năng nghiêm trọng ở dưới đoạn bị thương, mà còn tạo ra gánh nặng kinh tế không thể tưởng tượng cho sự phát triển xã hội. Exosome là những vật mang thông tin giao tiếp giữa tế bào có kích thước nano tồn tại ổn định trong hầu hết các sinh vật và loại tế bào. Nhờ vào khả năng vận chuyển protein, lipid và axit nucleic, exosome ảnh hưởng đến nhiều chức năng sinh lý và bệnh lý của các tế bào nhận và tế bào mẹ. Autophagy là một quá trình dựa vào con đường lysosomal để phân giải protein và bào quan trong tế bào và liên quan đến nhiều quá trình bệnh sinh. Exosome và autophagy đóng vai trò quan trọng trong việc duy trì cân bằng tế bào sau chấn thương tủy sống. Hiện nay, cơ chế phối hợp giữa exosome và autophagy đã thu hút nhiều sự chú ý trong hiệu quả ban đầu của chấn thương tủy sống. Trong bài tổng quan này, chúng tôi đã thảo luận về sự tương tác giữa autophagy và exosome từ góc độ cơ chế phân tử, điều này có thể cung cấp những hiểu biết mới cho ứng dụng điều trị sớm chấn thương tủy sống.

Từ khóa


Tài liệu tham khảo

Adnan M, Islam W, Zhang J, Zheng W, Lu GD (2019) Diverse role of SNARE protein Sec22 in vesicle trafficking, membrane fusion, and autophagy. Cells 8

Ahuja CS, Fehlings M (2016) Concise review: bridging the gap: novel neuroregenerative and neuroprotective strategies in spinal cord injury. Stem Cells Transl Med 5:914–924

Alizadeh J, Kochan MM, Stewart VD, Drewnik DA, Hannila SS, Ghavami S (2021) Inhibition of autophagy flux promotes secretion of chondroitin sulfate proteoglycans in primary rat astrocytes. Mol Neurobiol 58:6077–6091

Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJ, Cooper JM (2011) Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 42:360–367

Bader CA, Shandala T, Ng YS, Johnson IR, Brooks DA (2015) Atg9 is required for intraluminal vesicles in amphisomes and autolysosomes. Biol Open 4:1345–1355

Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14:677–685

Bankston AN, Forston MD, Howard RM, Andres KR, Smith AE, Ohri SS, Bates ML, Bunge MB, Whittemore SR (2019) Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination. Glia 67:1745–1759

Cao Y, Xu Y, Chen C, Xie H, Lu H, Hu J (2021) Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis. Stem Cell Res Ther 12:20

Casili G, Campolo M, Lanza M, Filippone A, Scuderi S, Messina S, Ardizzone A, Esposito E, Paterniti I (2020) Role of ABT888, a novel poly(ADP-ribose) polymerase (PARP) inhibitor in countering autophagy and apoptotic processes associated to spinal cord injury. Mol Neurobiol 57:4394–4407

Chen G, Li J, Wang Z, Liu W (2020a) Ezetimibe protects against spinal cord injury by regulating autophagy and apoptosis through inactivation of PI3K/AKT/mTOR signaling. Am J Transl Res 12:2685–2694

Chen HC, Fong TH, Hsu PW, Chiu WT (2013) Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion, anti-inflammation, and neuroprotection. J Surg Res 179:e203-210

Chen J, Zhang C, Li S, Li Z, Lai X, Xia Q (2021a) Exosomes derived from nerve stem cells loaded with FTY720 promote the recovery after spinal cord injury in rats by PTEN/AKT signal pathway. J Immunol Res 2021:8100298

Chen N, Zhou P, Liu X, Li J, Wan Y, Liu S, Wei F (2020b) Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury. Faseb j 34:6984–6998

Chen Y, Tian Z, He L, Liu C, Wang N, Rong L, Liu B (2021b) Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury. Stem Cell Res Ther 12:224

Chen YD, Fang YT, Cheng YL, Lin CF, Hsu LJ, Wang SY, Anderson R, Chang CP, Lin YS (2017) Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells. Sci Rep 7:5676

Cheng J, Chen Z, Liu C, Zhong M, Wang S, Sun Y, Wen H, Shu T (2021a) Bone mesenchymal stem cell-derived exosome-loaded injectable hydrogel for minimally invasive treatment of spinal cord injury. Nanomedicine (lond) 16:1567–1579

Cheng X, Xiao F, Xie R, Hu H, Wan Y (2021b) Alternate thermal stimulation ameliorates thermal sensitivity and modulates calbindin-D 28K expression in lamina I and II and dorsal root ganglia in a mouse spinal cord contusion injury model. Faseb j 35:e21173

Cho MH, Cho K, Kang HJ, Jeon EY, Kim HS, Kwon HJ, Kim HM, Kim DH, Yoon SY (2014) Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy 10:1761–1775

Cong Y, Wang C, Wang J, Li H, Li Q (2020) NT-3 promotes oligodendrocyte proliferation and nerve function recovery after spinal cord injury by inhibiting autophagy pathway. J Surg Res 247:128–135

Dupont N, Jiang S, Pilli M, Ornatowski W, Bhattacharya D, Deretic V (2011) Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β. Embo j 30:4701–4711

Fader CM, Sánchez D, Furlán M, Colombo MI (2008) Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic 9:230–250

Fan H, Zhang K, Shan L, Kuang F, Chen K, Zhu K, Ma H, Ju G, Wang YZ (2016) Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury. Mol Neurodegener 11:14

Fan Y, Li Y, Huang S, Xu H, Li H, Liu B (2020) Resveratrol-primed exosomes strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K signaling pathway. Neurosci Lett 736:135262

Fîlfan M, Sandu RE, Zăvăleanu AD, GreşiŢă A, Glăvan DG, Olaru DG, Popa-Wagner A (2017) Autophagy in aging and disease. Rom J Morphol Embryol 58:27–31

Florey O, Kim SE, Sandoval CP, Haynes CM, Overholtzer M (2011) Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol 13:1335–1343

Gao K, Niu J, Dang X (2020a) Neuroprotection of melatonin on spinal cord injury by activating autophagy and inhibiting apoptosis via SIRT1/AMPK signaling pathway. Biotechnol Lett 42:2059–2069

Gao K, Niu J, Dang X (2020b) Wnt-3a improves functional recovery through autophagy activation via inhibiting the mTOR signaling pathway after spinal cord injury. Neurosci Lett 737:135305

Gao ZS, Zhang CJ, Xia N, Tian H, Li DY, Lin JQ, Mei XF, Wu C (2021) Berberine-loaded M2 macrophage-derived exosomes for spinal cord injury therapy. Acta Biomater 126:211–223

Gaudet AD, Fonken LK (2018) Glial cells shape pathology and repair after spinal cord injury. Neurotherapeutics 15:554–577

Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221:3–12

Goncalves MB, Wu Y, Clarke E, Grist J, Hobbs C, Trigo D, Jack J, Corcoran JPT (2019) Regulation of myelination by exosome associated retinoic acid release from NG2-positive cells. J Neurosci 39:3013–3027

Gu J, Jin ZS, Wang CM, Yan XF, Mao YQ, Chen S (2020) Bone marrow mesenchymal stem cell-derived exosomes improves spinal cord function after injury in rats by activating autophagy. Drug Des Devel Ther 14:1621–1631

Guo H, Chitiprolu M, Roncevic L, Javalet C, Hemming FJ, Trung MT, Meng L, Latreille E, Tanese de Souza C, McCulloch D, Baldwin RM, Auer R, Côté J, Russell RC, Sadoul R, Gibbings D (2017) Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev Cell 43:716-730.e717

Guo H, Sadoul R, Gibbings D (2018) Autophagy-independent effects of autophagy-related-5 (Atg5) on exosome production and metastasis. Mol Cell Oncol 5:e1445941

Guo Y, Hong W, Wang X, Zhang P, Körner H, Tu J, Wei W (2019) MicroRNAs in microglia: how do microRNAs affect activation, inflammation, polarization of microglia and mediate the interaction between microglia and glioma? Front Mol Neurosci 12:125

Henne WM, Stenmark H, Emr SD (2013) Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol 5

Herbert FJ, Bharathi D, Suresh S, David E, Kumar S (2022) Regenerative potential of stem cell-derived extracellular vesicles in spinal cord injury (SCI). Curr Stem Cell Res Ther 17:280–293

Hervera A, De Virgiliis F, Palmisano I, Zhou L, Tantardini E, Kong G, Hutson T, Danzi MC, Perry RB, Santos CXC, Kapustin AN, Fleck RA, Del Río JA, Carroll T, Lemmon V, Bixby JL, Shah AM, Fainzilber M, Di Giovanni S (2018) Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons. Nat Cell Biol 20:307–319

Hessvik NP, Llorente A (2018) Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 75:193–208

Huang JH, Xu Y, Yin XM, Lin FY (2020) Exosomes derived from miR-126-modified MSCs promote angiogenesis and neurogenesis and attenuate apoptosis after spinal cord injury in rats. Neuroscience 424:133–145

Huang W, Qu M, Li L, Liu T, Lin M, Yu X (2021a) SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats. Stem Cell Res Ther 12:334

Huang Y, Ren H, Gao X, Cai D, Shan H, Bai J, Sheng L, Jin Y, Zhou X (2021b) Amlodipine improves spinal cord injury repair by inhibiting motoneuronal apoptosis through autophagy upregulation. Spine (Phila Pa 1976)

Hurley JH (2015) ESCRTs are everywhere. EMBO J 34:2398–2407

Hurwitz SN, Cheerathodi MR, Nkosi D, York SB, Meckes DG (2018) Tetraspanin CD63 bridges autophagic and endosomal processes to regulate exosomal secretion and intracellular signaling of Epstein-Barr virus LMP1. J Virol 92

Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y (2000) A ubiquitin-like system mediates protein lipidation. Nature 408:488–492

Jia X, Huang G, Wang S, Long M, Tang X, Feng D, Zhou Q (2021a) Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis. Bone Joint Res 10:328–339

Jia Y, Lu T, Chen Q, Pu X, Ji L, Yang J, Luo C (2021b) Exosomes secreted from sonic hedgehog-modified bone mesenchymal stem cells facilitate the repair of rat spinal cord injuries. Acta Neurochir (wien) 163:2297–2306

Jiang D, Gong F, Ge X, Lv C, Huang C, Feng S, Zhou Z, Rong Y, Wang J, Ji C, Chen J, Zhao W, Fan J, Liu W, Cai W (2020) Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes. J Nanobiotechnology 18:105

Kang J, Li Z, Zhi Z, Wang S, Xu G (2019) MiR-21 derived from the exosomes of MSCs regulates the death and differentiation of neurons in patients with spinal cord injury. Gene Ther 26:491–503

Kanno H, Ozawa H, Sekiguchi A, Yamaya S, Itoi E (2011) Induction of autophagy and autophagic cell death in damaged neural tissue after acute spinal cord injury in mice. Spine 36:E1427-1434

Kanno H, Ozawa H, Sekiguchi A, Yamaya S, Tateda S, Yahata K, Itoi E (2012) The role of mTOR signaling pathway in spinal cord injury. Cell Cycle (georgetown, Tex) 11:3175–3179

Kenific CM, Zhang H, Lyden D (2021) An exosome pathway without an ESCRT. Cell Res 31:105–106

Khan NZ, Cao T, He J, Ritzel RM, Li Y, Henry RJ, Colson C, Stoica BA, Faden AI, Wu J (2021) Spinal cord injury alters microRNA and CD81+ exosome levels in plasma extracellular nanoparticles with neuroinflammatory potential. Brain Behav Immun 92:165–183

Kim GU, Sung SE, Kang KK, Choi JH, Lee S, Sung M, Yang, SY, Kim SK, Kim YI, Lim JH, Seo MS, Lee GW (2021) Therapeutic potential of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles for the treatment of spinal cord injury. Int J Mol Sci 22

Kimura T, Jia J, Kumar S, Choi SW, Gu Y, Mudd M, Dupont N, Jiang S, Peters R, Farzam F, Jain A, Lidke KA, Adams CM, Johansen T, Deretic V (2017) Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy. EMBO J 36:42–60

Kong FL, Wang XP, Li YN, Wang HX (2018) The role of exosomes derived from cerebrospinal fluid of spinal cord injury in neuron proliferation in vitro. Artif Cells Nanomed Biotechnol 46:200–205

Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Théry C (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA 113:E968-977

Kowal J, Tkach M, Théry C (2014) Biogenesis and secretion of exosomes. Curr Opin Cell Biol 29:116–125

Lamb CA, Yoshimori T, Tooze SA (2013) The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol 14:759–774

Li C, Li X, Zhao B, Wang C (2020a) Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury. Arch Physiol Biochem 126:369–375

Li D, Qu J, Yuan X, Zhuang S, Wu H, Chen R, Wu J, Zhang M, Ying L (2022) Mesenchymal stem cells alleviate renal fibrosis and inhibit autophagy via exosome transfer of miRNA-122a. Stem Cells Int 2022:1981798

Li R, Zhao K, Ruan Q, Meng C, Yin F (2020b) Bone marrow mesenchymal stem cell-derived exosomal microRNA-124-3p attenuates neurological damage in spinal cord ischemia-reperfusion injury by downregulating Ern1 and promoting M2 macrophage polarization. Arthritis Res Ther 22:75

Li W, Yao S, Li H, Meng Z, Sun X (2021a) Curcumin promotes functional recovery and inhibits neuronal apoptosis after spinal cord injury through the modulation of autophagy. J Spinal Cord Med 44:37–45

Li X, Kang J, Lv H, Liu R, Chen J, Zhang Y, Zhang Y, Yu G, Zhang X, Ning B (2021b) CircPrkcsh, a circular RNA, contributes to the polarization of microglia towards the M1 phenotype induced by spinal cord injury and acts via the JNK/p38 MAPK pathway. Faseb j 35:e22014

Li Y, Guo Y, Fan Y, Tian H, Li K, Mei X (2019) Melatonin enhances autophagy and reduces apoptosis to promote locomotor recovery in spinal cord injury via the PI3K/AKT/mTOR signaling pathway. Neurochem Res 44:2007–2019

Li Y, Shen PP, Wang B (2021c) Induced pluripotent stem cell technology for spinal cord injury: a promising alternative therapy. Neural Regen Res 16:1500–1509

Li Y, Xiang J, Zhang J, Lin J, Wu Y, Wang X (2020c) Inhibition of Brd4 by JQ1 promotes functional recovery from spinal cord injury by activating autophagy. Front Cell Neurosci 14:555591

Li Y, Zhang J, Zhou K, Xie L, Xiang G, Fang M, Han W, Wang X, Xiao J (2021d) Elevating sestrin2 attenuates endoplasmic reticulum stress and improves functional recovery through autophagy activation after spinal cord injury. Cell Biol Toxicol 37:401–419

Lin J, Pan X, Huang C, Gu M, Chen X, Zheng X, Shao Z, Hu S, Wang B, Lin H, Wu Y, Tian N, Wu Y, Gao W, Zhou Y, Zhang X, Wang X (2020) Dual regulation of microglia and neurons by astragaloside IV-mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury. J Cell Mol Med 24:671–685

Lipinski MM, Wu J, Faden AI, Sarkar C (2015) Function and mechanisms of autophagy in brain and spinal cord trauma. Antioxid Redox Signal 23:565–577

Liu B, Zheng W, Dai L, Fu S, Shi E (2022) Bone marrow mesenchymal stem cell derived exosomal miR-455-5p protects against spinal cord ischemia reperfusion injury. Tissue Cell 74:101678

Liu J, Li R, Huang Z, Lin J, Ji W, Huang Z, Liu Q, Wu X, Wu X, Jiang H, Ye Y, Zhu Q (2020a) Rapamycin preserves neural tissue, promotes Schwann cell myelination and reduces glial scar formation after hemi-contusion spinal cord injury in mice. Front Mol Neurosci 13:574041

Liu J, Zhang Y, Liu A, Wang J, Li L, Chen X, Gao X, Xue Y, Zhang X, Liu Y (2016) Distinct dasatinib-induced mechanisms of apoptotic response and exosome release in imatinib-resistant human chronic myeloid leukemia cells. Int J Mol Sci 17:531

Liu S, Xie YY, Wang LD, Tai CX, Chen D, Mu D, Cui YY, Wang B (2021a) A multi-channel collagen scaffold loaded with neural stem cells for the repair of spinal cord injury. Neural Regen Res 16:2284–2292

Liu W, Rong Y, Wang J, Zhou Z, Ge X, Ji C, Jiang D, Gong F, Li L, Chen J, Zhao S, Kong F, Gu C, Fan J, Cai W (2020b) Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization. J Neuroinflammation 17:47

Liu W, Tang P, Wang J, Ye W, Ge X, Rong Y, Ji C, Wang Z, Bai J, Fan J, Yin G, Cai W (2021b) Extracellular vesicles derived from melatonin-preconditioned mesenchymal stem cells containing USP29 repair traumatic spinal cord injury by stabilizing NRF2. J Pineal Res 71:e12769

Luo Y, Xu T, Liu W, Rong Y, Wang J, Fan J, Yin G, Cai W (2021) Exosomes derived from GIT1-overexpressing bone marrow mesenchymal stem cells promote traumatic spinal cord injury recovery in a rat model. Int J Neurosci 131:170–182

Ma K, Xu H, Zhang J, Zhao F, Liang H, Sun H, Li P, Zhang S, Wang R, Chen X (2019) Insulin-like growth factor-1 enhances neuroprotective effects of neural stem cell exosomes after spinal cord injury via an miR-219a-2-3p/YY1 mechanism. Aging 11:12278–12294

Martinez J, Malireddi RK, Lu Q, Cunha LD, Pelletier S, Gingras S, Orchard R, Guan JL, Tan H, Peng J, Kanneganti TD, Virgin HW, Green DR (2015) Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol 17:893–906

Matsui T, Osaki F, Hiragi S, Sakamaki Y, Fukuda M (2021) ALIX and ceramide differentially control polarized small extracellular vesicle release from epithelial cells. EMBO Rep 22:e51475

Matsuura A, Tsukada M, Wada Y, Ohsumi Y (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192:245–250

Medvedev R, Hildt E, Ploen D (2017) Look who’s talking-the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles. Cell Biol Toxicol 33:211–231

Murrow L, Malhotra R, Debnath J (2015) ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. Nat Cell Biol 17:300–310

Nicaise AM, D’Angelo A, Ionescu RB, Krzak G, Willis CM, Pluchino S (2022) The role of neural stem cells in regulating glial scar formation and repair. Cell Tissue Res 387:399–414

Nie H, Jiang Z (2021) Bone mesenchymal stem cell-derived extracellular vesicles deliver microRNA-23b to alleviate spinal cord injury by targeting toll-like receptor TLR4 and inhibiting NF-κB pathway activation. Bioengineered 12:8157–8172

Orr MB, Gensel JC (2018) Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses. Neurotherapeutics 15:541–553

Pan D, Li Y, Yang F, Lv Z, Zhu S, Shao Y, Huang Y, Ning G, Feng S (2021) Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury. J Neuroinflammation 18:172

Pan D, Zhu S, Zhang W, Wei Z, Yang F, Guo Z, Ning G, Feng S (2022) Autophagy induced by Schwann cell-derived exosomes promotes recovery after spinal cord injury in rats. Biotechnol Lett 44:129–142

Park JM, Jung CH, Seo M, Otto NM, Grunwald D, Kim KH, Moriarity B, Kim YM, Starker C, Nho RS, Voytas D, Kim DH (2016) The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy 12:547–564

Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383

Ray SK (2020) Modulation of autophagy for neuroprotection and functional recovery in traumatic spinal cord injury. Neural Regen Res 15:1601–1612

Ren XD, Wan CX, Niu YL (2019a) Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury. FEBS Open Bio 9:1223–1231

Ren ZW, Zhou JG, Xiong ZK, Zhu FZ, Guo XD (2019b) Effect of exosomes derived from MiR-133b-modified ADSCs on the recovery of neurological function after SCI. Eur Rev Med Pharmacol Sci 23:52–60

Rong Y, Fan J, Ji C, Wang Z, Ge X, Wang J, Ye W, Yin G, Cai W, Liu W (2021a) USP11 regulates autophagy-dependent ferroptosis after spinal cord ischemia-reperfusion injury by deubiquitinating Beclin 1. Cell Death Differ

Rong Y, Ji C, Wang Z, Ge X, Wang J, Ye W, Tang P, Jiang D, Fan J, Yin G, Liu W, Cai W (2021b) Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury. J Neuroinflammation 18:196

Rong Y, Liu W, Lv C, Wang J, Luo Y, Jiang D, Li L, Zhou Z, Zhou W, Li Q, Yin G, Yu L, Fan J, Cai W (2019a) Neural stem cell small extracellular vesicle-based delivery of 14-3-3t reduces apoptosis and neuroinflammation following traumatic spinal cord injury by enhancing autophagy by targeting Beclin-1. Aging 11:7723–7745

Rong Y, Liu W, Wang J, Fan J, Luo Y, Li L, Kong F, Chen J, Tang P, Cai W (2019b) Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy. Cell Death Dis 10:340

Saraswat Ohri S, Bankston AN, Mullins SA, Liu Y, Andres KR, Beare JE, Howard RM, Burke DA, Riegler AS, Smith AE, Hetman M, Whittemore SR (2018) Blocking autophagy in oligodendrocytes limits functional recovery after spinal cord injury. J Neurosci 38:5900–5912

Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

Scott CC, Vacca F, Gruenberg J (2014) Endosome maturation, transport and functions. Semin Cell Dev Biol 31:2–10

Shao M, Jin M, Xu S, Zheng C, Zhu W, Ma X, Lv F (2020) Exosomes from long noncoding RNA-Gm37494-ADSCs repair spinal cord injury via shifting microglial M1/M2 polarization. Inflammation 43:1536–1547

Shrivastava S, Devhare P, Sujijantarat N, Steele R, Kwon YC, Ray R, Ray RB (2016) Knockdown of autophagy inhibits infectious hepatitis C virus release by the exosomal pathway. J Virol 90:1387–1396

Tahmasebi F, Barati S (2022) Effects of mesenchymal stem cell transplantation on spinal cord injury patients. Cell Tissue Res

Tang YJ, Li K, Yang CL, Huang K, Zhou J, Shi Y, Xie KG, Liu J (2019) Bisperoxovanadium protects against spinal cord injury by regulating autophagy via activation of ERK1/2 signaling. Drug Des Devel Ther 13:513–521

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, Ayre DC, Bach JM, Bachurski D, Baharvand H, Balaj L, Baldacchino S, Bauer NN, Baxter AA, Bebawy M, Beckham C, Bedina Zavec A, Benmoussa A, Berardi AC, Bergese P, Bielska E, Blenkiron C, Bobis-Wozowicz S, Boilard E, Boireau W, Bongiovanni A, Borràs FE, Bosch S, Boulanger CM, Breakefield X, Breglio AM, Brennan M, Brigstock DR, Brisson A, Broekman ML, Bromberg JF, Bryl-Górecka P, Buch S, Buck AH, Burger D, Busatto S, Buschmann D, Bussolati B, Buzás EI, Byrd JB, Camussi G, Carter DR, Caruso S, Chamley LW, Chang YT, Chen C, Chen S, Cheng L, Chin AR, Clayton A, Clerici SP, Cocks A, Cocucci E, Coffey RJ, Cordeiro-da-Silva A, Couch Y, Coumans FA, Coyle B, Crescitelli R, Criado MF, D’Souza-Schorey C, Das S, Datta Chaudhuri A, de Candia P, De Santana EF, De Wever O, Del Portillo HA, Demaret T, Deville S, Devitt A, Dhondt B, Di Vizio D, Dieterich LC, Dolo V, Dominguez Rubio AP, Dominici M, Dourado MR, Driedonks TA, Duarte FV, Duncan HM, Eichenberger RM, Ekström K, El Andaloussi S, Elie-Caille C, Erdbrügger U, Falcón-Pérez JM, Fatima F, Fish JE, Flores-Bellver M, Försönits A, Frelet-Barrand A, Fricke F, Fuhrmann G, Gabrielsson S, Gámez-Valero A, Gardiner C, Gärtner K, Gaudin R, Gho YS, Giebel B, Gilbert C, Gimona M, Giusti I, Goberdhan DC, Görgens A, Gorski SM, Greening DW, Gross JC, Gualerzi A, Gupta GN, Gustafson D, Handberg A, Haraszti RA, Harrison P, Hegyesi H, Hendrix A, Hill AF, Hochberg FH, Hoffmann KF, Holder B, Holthofer H, Hosseinkhani B, Hu G, Huang Y, Huber V, Hunt S, Ibrahim AG, Ikezu T, Inal JM, Isin M, Ivanova A, Jackson HK, Jacobsen S, Jay SM, Jayachandran M, Jenster G, Jiang L, Johnson SM, Jones JC, Jong A, Jovanovic-Talisman T, Jung S, Kalluri R, Kano SI, Kaur S, Kawamura Y, Keller ET, Khamari D, Khomyakova E, Khvorova A, Kierulf P, Kim KP, Kislinger T, Klingeborn M, Klinke DJ, Kornek M, Kosanović MM, Kovács ÁF, Krämer-Albers EM, Krasemann S, Krause M, Kurochkin IV, Kusuma GD, Kuypers S, Laitinen S, Langevin SM, Languino LR, Lannigan J, Lässer C, Laurent LC, Lavieu G, Lázaro-Ibáñez E, Le Lay S, Lee MS, Lee YXF, Lemos DS, Lenassi M, Leszczynska A, Li IT, Liao K, Libregts SF, Ligeti E, Lim R, Lim SK, Linē A, Linnemannstöns K, Llorente A, Lombard CA, Lorenowicz MJ, Lörincz ÁM, Lötvall J, Lovett J, Lowry MC, Loyer X, Lu Q, Lukomska B, Lunavat TR, Maas SL, Malhi H, Marcilla A, Mariani J, Mariscal J, Martens-Uzunova ES, Martin-Jaular L, Martinez MC, Martins VR, Mathieu M, Mathivanan S, Maugeri M, McGinnis LK, McVey MJ, Meckes DG, Meehan KL, Mertens I, Minciacchi VR, Möller A, Møller Jørgensen M, Morales-Kastresana A, Morhayim J, Mullier F, Muraca M, Musante L, Mussack V, Muth DC, Myburgh KH, Najrana T, Nawaz M, Nazarenko I, Nejsum P, Neri C, Neri T, Nieuwland R, Nimrichter L, Nolan JP., Nolte-’t Hoen EN, Noren Hooten N, O’Driscoll L, O’Grady T, O’Loghlen A, Ochiya T, Olivier M, Ortiz A, Ortiz LA, Osteikoetxea X, Østergaard O, Ostrowski M, Park J, Pegtel DM, Peinado H, Perut F, Pfaffl MW, Phinney DG, Pieters BC, Pink RC, Pisetsky DS, Pogge von Strandmann E, Polakovicova I, Poon IK, Powell BH, Prada I, Pulliam L, Quesenberry P, Radeghieri A, Raffai RL, Raimondo S, Rak J, Ramirez MI, Raposo G, Rayyan MS, Regev-Rudzki N, Ricklefs FL, Robbins PD, Roberts DD, Rodrigues SC, Rohde E, Rome S, Rouschop KM, Rughetti A, Russell AE, Saá P, Sahoo S, Salas-Huenuleo E, Sánchez C, Saugstad JA, Saul MJ, Schiffelers RM, Schneider R, Schøyen TH, Scott A, Shahaj E, Sharma S, Shatnyeva O, Shekari F, Shelke GV, Shetty AK, Shiba K, Siljander PR, Silva AM, Skowronek A, Snyder OL, Soares RP, Sódar BW, Soekmadji C, Sotillo J, Stahl PD, Stoorvogel W, Stott SL, Strasser EF, Swift S, Tahara H, Tewari M, Timms K, Tiwari S, Tixeira R, Tkach M, Toh WS, Tomasini R, Torrecilhas AC, Tosar JP, Toxavidis V, Urbanelli L, Vader P, van Balkom BW, van der Grein SG, Van Deun J, van Herwijnen MJ, Van Keuren-Jensen K, van Niel G, van Royen ME, van Wijnen AJ, Vasconcelos MH, Vechetti IJ, Veit TD, Vella LJ, Velot É, Verweij FJ, Vestad B, Viñas JL, Visnovitz T, Vukman KV, Wahlgren J, Watson DC, Wauben MH, Weaver A, Webber JP, Weber V, Wehman AM, Weiss DJ, Welsh JA, Wendt S, Wheelock AM, Wiener Z, Witte L, Wolfram J, Xagorari A, Xander P, Xu J, Yan X, Yáñez-Mó M, Yin H, Yuana Y, Zappulli V, Zarubova J, Žėkas V, Zhang JY, Zhao Z, Zheng L, Zheutlin AR, Zickler AM, Zimmermann P, Zivkovic AM, Zocco D, Zuba-Surma EK (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 7:1535750

Tian H, Zhao H, Mei X, Li D, Lin J, Lin S, Song C (2021) Resveratrol inhibits LPS-induced apoptosis in VSC4.1 motoneurons through enhancing SIRT1-mediated autophagy. Iran J Basic Med Sci 24:38–43

Tooze SA, Abada A, Elazar Z (2014) Endocytosis and autophagy: exploitation or cooperation? Cold Spring Harb Perspect Biol 6:a018358

Tran AP, Warren PM, Silver J (2022) New insights into glial scar formation after spinal cord injury. Cell Tissue Res 387:319–336

Tschuschke M, Kocherova I, Bryja A, Mozdziak P, Angelova Volponi A, Janowicz K, Sibiak R, Piotrowska-Kempisty H, Iżycki D, Bukowska D, Antosik P, Shibli JA, Dyszkiewicz-Konwińska M, Kempisty B (2020) Inclusion biogenesis, methods of isolation and clinical application of human cellular exosomes. J Clin Med 9

Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174

van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G (2011) The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell 21:708–721

Varderidou-Minasian S, Lorenowicz MJ (2020) Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics 10:5979–5997

Vietri M, Radulovic M, Stenmark H (2020) The many functions of ESCRTs. Nat Rev Mol Cell Biol 21:25–42

Villarroya-Beltri C, Baixauli F, Mittelbrunn M, Fernández-Delgado I, Torralba D, Moreno-Gonzalo O, Baldanta S, Enrich C, Guerra S, Sánchez-Madrid F (2016) ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun 7:13588

Walker CL, Walker MJ, Liu NK, Risberg EC, Gao X, Chen J, Xu XM (2012) Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury. PLoS ONE 7:e30012

Wan B, Li C, Wang M, Kong F, Ding Q, Zhang C, Liu H, Qian D, Deng W, Chen J, Tang P, Wang Q, Zhao S, Zhou Z, Xu T, Huang Y, Gu J, Fan J, Yin G (2021) GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris. Aging 13:7067–7083

Wang C, Wang Q, Lou Y, Xu J, Feng Z, Chen Y, Tang Q, Zheng G, Zhang Z, Wu Y, Tian N, Zhou Y, Xu H, Zhang X (2018) Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation. J Cell Mol Med 22:1148–1166

Wang F, Chang S, Li J, Wang D, Li H, He X (2021a) Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis. Cell Tissue Res 384:301–312

Wang J, Rong Y, Ji C, Lv C, Jiang D, Ge X, Gong F, Tang P, Cai W, Liu W, Fan J (2020) MicroRNA-421-3p-abundant small extracellular vesicles derived from M2 bone marrow-derived macrophages attenuate apoptosis and promote motor function recovery via inhibition of mTOR in spinal cord injury. J Nanobiotechnology 18:72

Wang Y, Lai X, Wu D, Liu B, Wang N, Rong L (2021b) Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional recovery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats. Stem Cell Res Ther 12:117

Wang Y, Xiong M, Wang M, Chen H, Li W, Zhou X (2021c) Quercetin promotes locomotor function recovery and axonal regeneration through induction of autophagy after spinal cord injury. Clin Exp Pharmacol Physiol 48:1642–1652

Wei D, Zhan W, Gao Y, Huang L, Gong R, Wang W, Zhang R, Wu Y, Gao S, Kang T (2021) RAB31 marks and controls an ESCRT-independent exosome pathway. Cell Res 31:157–177

Wu C, Chen H, Zhuang R, Zhang H, Wang Y, Hu X, Xu Y, Li J, Li Y, Wang X, Xu H, Ni W, Zhou K (2021) Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway. Int J Biol Sci 17:1138–1152

Xi L, Peng M, Liu S, Liu Y, Wan X, Hou Y, Qin Y, Yang L, Chen S, Zeng H, Teng Y, Cui X, Liu M (2021) Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion. J Extracell Vesicles 10:e12146

Xiao X, Li W, Rong D, Xu Z, Zhang Z, Ye H, Xie L, Wu Y, Zhang Y, Wang X (2021) Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis. Cell Death Discov 7:212

Xiong Y, Xia Y, Deng J, Yan X, Ke J, Zhan J, Zhang Z, Wang Y (2020) Direct peritoneal resuscitation with pyruvate protects the spinal cord and induces autophagy via regulating PHD2 in a rat model of spinal cord ischemia-reperfusion injury. Oxid Med Cell Longev 2020:4909103

Xu C, Mao L, Tian H, Lin S, Zhao X, Lin J, Li D, Li X, Mei X (2021a) MICAL1 (molecule interacting with CasL 1) protects oligodendrocyte cells from oxidative injury through regulating apoptosis, autophagy in spinal cord injury. Neurosci Lett 750:135712

Xu G, Ao R, Zhi Z, Jia J, Yu B (2019) miR-21 and miR-19b delivered by hMSC-derived EVs regulate the apoptosis and differentiation of neurons in patients with spinal cord injury. J Cell Physiol 234:10205–10217

Xu Y, Hu X, Li F, Zhang H, Lou J, Wang X, Wang H, Yin L, Ni W, Kong J, Wang X, Li Y, Zhou K, Xu H (2021b) GDF-11 protects the traumatically injured spinal cord by suppressing pyroptosis and necroptosis via TFE3-mediated autophagy augmentation. Oxid Med Cell Longev 2021:8186877

Xu Z, Li Z (2020) Experimental study on the role of apelin-13 in alleviating spinal cord ischemia reperfusion injury through suppressing autophagy. Drug Des Devel Ther 14:1571–1581

Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colás E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Krämer-Albers EM, Laitinen S, Lässer C, Lener T, Ligeti E, Linē A, Lipps G, Llorente A, Lötvall J, Manček-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-’t Hoen EN, Nyman TA, O’Driscoll L, Olivan M, Oliveira C, Pállinger É, Del Portillo HA, Reventós J, Rigau M, Rohde E, Sammar M, Sánchez-Madrid F, Santarém N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066

Ye J, Jiang Z, Chen X, Liu M, Li J, Liu N (2017) The role of autophagy in pro-inflammatory responses of microglia activation via mitochondrial reactive oxygen species in vitro. J Neurochem 142:215–230

Ye LX, An NC, Huang P, Li DH, Zheng ZL, Ji H, Li H, Chen DQ, Wu YQ, Xiao J, Xu K, Li XK, Zhang HY (2021) Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury. Neural Regen Res 16:765–771

Yin J, Yin Z, Wang B, Zhu C, Sun C, Liu X, Gong G (2019) Angiopoietin-1 protects spinal cord ischemia and reperfusion injury by inhibiting autophagy in rats. Neurochem Res 44:2746–2754

Yuan W, He X, Morin D, Barrière G, Liu X, Li J, Zhu Y (2021) Autophagy induction contributes to the neuroprotective impact of intermittent fasting on the acutely injured spinal cord. J Neurotrauma 38:373–384

Zhai X, Chen K, Yang H, Li B, Zhou T, Wang H, Zhou H, Chen S, Zhou X, Wei X, Bai Y, Li M (2021) Extracellular vesicles derived from CD73 modified human umbilical cord mesenchymal stem cells ameliorate inflammation after spinal cord injury. J Nanobiotechnology 19:274

Zhang A, Bai Z, Yi W, Hu Z, Hao J (2021a) Overexpression of miR-338-5p in exosomes derived from mesenchymal stromal cells provides neuroprotective effects by the Cnr1/Rap1/Akt pathway after spinal cord injury in rats. Neurosci Lett 761:136124

Zhang B, Lin F, Dong J, Liu J, Ding Z, Xu J (2021b) Peripheral macrophage-derived exosomes promote repair after spinal cord injury by inducing local anti-inflammatory type microglial polarization via increasing autophagy. Int J Biol Sci 17:1339–1352

Zhang C, Li D, Hu H, Wang Z, An J, Gao Z, Zhang K, Mei X, Wu C, Tian H (2021c) Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury. J Nanobiotechnology 19:373

Zhang C, Ma S, Zhao X, Wen B, Sun P, Fu Z (2021d) Upregulation of antioxidant and autophagy pathways via NRF2 activation protects spinal cord neurons from ozone damage. Mol Med Rep 23

Zhang D, Yu D, Mei X, Lv G (2020) Liraglutide provides neuroprotection by regulating autophagy through the AMPK-FOXO3 signaling pathway in a spinal contusion injury rat model. Neurosci Lett 720:134747

Zhang L, Fan C, Hao W, Zhuang Y, Liu X, Zhao Y, Chen B, Xiao Z, Chen Y, Dai J (2021e) NSCs migration promoted and drug delivered exosomes-collagen scaffold via a bio-specific peptide for one-step spinal cord injury repair. Adv Healthc Mater 10:e2001896

Zhang M, Wang L, Huang S, He X (2021f) Exosomes with high level of miR-181c from bone marrow-derived mesenchymal stem cells inhibit inflammation and apoptosis to alleviate spinal cord injury. J Mol Histol 52:301–311

Zheng HC (2017) The molecular mechanisms of chemoresistance in cancers. Oncotarget 8:59950–59964

Zheng Z, Zhou Y, Ye L, Lu Q, Zhang K, Zhang J, Xie L, Wu Y, Xu K, Zhang H, Xiao J (2020) Histone deacetylase 6 inhibition restores autophagic flux to promote functional recovery after spinal cord injury. Exp Neurol 324:113138

Zhong D, Cao Y, Li CJ, Li M, Rong ZJ, Jiang L, Guo Z, Lu HB, Hu JZ (2020a) Neural stem cell-derived exosomes facilitate spinal cord functional recovery after injury by promoting angiogenesis. Exp Biol Med (maywood) 245:54–65

Zhong L, Fang S, Wang AQ, Zhang ZH, Wang T, Huang W, Zhou HX, Zhang H, Yin ZS (2022) Identification of the Fosl1/AMPK/autophagy axis involved in apoptotic and inflammatory effects following spinal cord injury. Int Immunopharmacol 103:108492

Zhong L, Zhang H, Ding ZF, Li J, Lv JW, Pan ZJ, Xu DX, Yin ZS (2020b) Erythropoietin-induced autophagy protects against spinal cord injury and improves neurological function via the extracellular-regulated protein kinase signaling pathway. Mol Neurobiol 57:3993–4006

Zhou J, Li Z, Zhao Q, Wu T, Zhao Q, Cao Y (2021a) Knockdown of SNHG1 alleviates autophagy and apoptosis by regulating miR-362-3p/Jak2/stat3 pathway in LPS-injured PC12 cells. Neurochem Res 46:945–956

Zhou K, Chen H, Xu H, Jia X (2021b) Trehalose augments neuron survival and improves recovery from spinal cord injury via mTOR-independent activation of autophagy. Oxid Med Cell Longev 2021:8898996

Zhou K, Zheng Z, Li Y, Han W, Zhang J, Mao Y, Chen H, Zhang W, Liu M, Xie L, Zhang H, Xu H, Xiao J (2020a) TFE3, a potential therapeutic target for spinal cord injury via augmenting autophagy flux and alleviating ER stress. Theranostics 10:9280–9302

Zhou R, Kan S, Cai S, Sun R, Yuan H, Yu B (2020b) Scopoletin activates adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway and improves functional recovery after spinal cord injury in rats. Pharmacology 105:349–359

Zhou X, Chu X, Yuan H, Qiu J, Zhao C, Xin D, Li T, Ma W, Wang H, Wang Z, Wang D (2019) Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis. Biomed Pharmacother 115:108818

Zhou Z, Hu B, Lyu Q, Xie T, Wang J, Cai Q (2020c) miR-384-5p promotes spinal cord injury recovery in rats through suppressing of autophagy and endoplasmic reticulum stress. Neurosci Lett 727:134937

Zhu N, Ruan J, Yang X, Huang Y, Jiang Y, Wang Y, Cai D, Geng Y, Fang M (2020a) Triptolide improves spinal cord injury by promoting autophagy and inhibiting apoptosis. Cell Biol Int 44:785–794

Zhu S, Ying Y, Ye J, Chen M, Wu Q, Dou H, Ni W, Xu H, Xu J (2021) AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats. Cell Death Dis 12:274

Zhu S, Ying Y, Ye L, Ying W, Ye J, Wu Q, Chen M, Zhu H, Li X, Dou H, Xu H, Wang Z, Xu J (2020b) Systemic administration of fibroblast growth factor 21 improves the recovery of spinal cord injury (SCI) in rats and attenuates SCI-induced autophagy. Front Pharmacol 11:628369