Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing

Doğruel, 2022, Management of diabetic foot ulcers and the challenging points: An endocrine view, World J. Diabetes, 13, 27, 10.4239/wjd.v13.i1.27 Grennan, 2019, Diabetic Foot Ulcers, JAMA, 321, 114, 10.1001/jama.2018.18323 Jeffcoate, 2018, Current Challenges and Opportunities in the Prevention and Management of Diabetic Foot Ulcers, Diabetes Care, 41, 645, 10.2337/dc17-1836 Louiselle, 2021, Macrophage polarization and diabetic wound healing, Transl. Res., 236, 109, 10.1016/j.trsl.2021.05.006 Wolf, 2021, Macrophage-mediated inflammation in diabetic wound repair, Semin. Cell Dev. Biol., 119, 111, 10.1016/j.semcdb.2021.06.013 Sharma, 2021, NLRP3 inflammasome in cancer and metabolic diseases, Nat. Immunol., 22, 550, 10.1038/s41590-021-00886-5 Paik, 2021, An update on the regulatory mechanisms of NLRP3 inflammasome activation, Cell. Mol. Immunol., 18, 1141, 10.1038/s41423-021-00670-3 Spel, 2020, Inflammasomes contributing to inflammation in arthritis, Immunol. Rev., 294, 48, 10.1111/imr.12839 Jäger, 2020, Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis, Nat. Commun., 11, 4243, 10.1038/s41467-020-17749-6 Renaudin, 2020, Gout and pseudo-gout-related crystals promote GLUT1-mediated glycolysis that governs NLRP3 and interleukin-1beta activation on macrophages, Ann. Rheum. Dis., 79, 1506, 10.1136/annrheumdis-2020-217342 Martinon, 2006, Gout-associated uric acid crystals activate the NALP3 inflammasome, Nature, 440, 237, 10.1038/nature04516 Ding, 2022, Relevance of NLRP3 Inflammasome-Related Pathways in the Pathology of Diabetic Wound Healing and Possible Therapeutic Targets, Oxid. Med. Cell. Longev., 2022, 10.1155/2022/9687925 Mirza, 2014, Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice, Diabetes, 63, 1103, 10.2337/db13-0927 Pereira, 2022, Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease, Med. Res. Rev., 42, 1518, 10.1002/med.21883 Pillon, 2021, Metabolic consequences of obesity and type 2 diabetes: Balancing genes and environment for personalized care, Cell, 184, 1530, 10.1016/j.cell.2021.02.012 Chou, 2022, Impact of intracellular innate immune receptors on immunometabolism, Cell. Mol. Immunol., 19, 337, 10.1038/s41423-021-00780-y SantaCruz-Calvo, 2022, Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities, Nat. Rev. Endocrinol., 18, 23, 10.1038/s41574-021-00575-1 Pearce, 2021, Metabolism as a driver of immunity, Nat. Rev. Immunol., 21, 618, 10.1038/s41577-021-00601-3 Liu, 2017, alpha-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming, Nat. Immunol., 18, 985, 10.1038/ni.3796 Runtsch, 2022, Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages, Cell Metab., 34, 487, 10.1016/j.cmet.2022.02.002 Hung, 2019, Amino acids and wound healing in people with limb-threatening diabetic foot ulcers, J. Diabetes Complications, 33 Floegel, 2013, Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach, Diabetes, 62, 639, 10.2337/db12-0495 van Spronsen, 2021, Phenylketonuria, Nat. Rev. Dis. Primers, 7, 36, 10.1038/s41572-021-00267-0 Czibik, 2021, Dysregulated Phenylalanine Catabolism Plays a Key Role in the Trajectory of Cardiac Aging, Circulation, 144, 559, 10.1161/CIRCULATIONAHA.121.054204 Liang, 2022, m(6)A reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin, Autophagy, 18, 1318, 10.1080/15548627.2021.1974175 Piazza, 2018, A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication, Cell, 172, 358, 10.1016/j.cell.2017.12.006 Katsnelson, 2016, NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx, Am. J. Physiol. Cell Physiol., 311, C83, 10.1152/ajpcell.00298.2015 Lin, 2021, Protein cysteine palmitoylation in immunity and inflammation, FEBS J., 288, 7043, 10.1111/febs.15728 Ahtiainen, 2003, Palmitoyl protein thioesterase 1 is targeted to the axons in neurons, J. Comp. Neurol., 455, 368, 10.1002/cne.10492 Lyly, 2008, Deficiency of the INCL protein Ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism, Hum. Mol. Genet., 17, 1406, 10.1093/hmg/ddn028 Bagh, 2017, Misrouting of v-ATPase subunit V0a1 dysregulates lysosomal acidification in a neurodegenerative lysosomal storage disease model, Nat. Commun., 8, 10.1038/ncomms14612 Zhou, 2022, Palmitoylation restricts SQSTM1/p62-mediated autophagic degradation of NOD2 to modulate inflammation, Cell Death Differ., 29, 1541, 10.1038/s41418-022-00942-z Yang, 2019, Palmitoylation stabilizes PD-L1 to promote breast tumor growth, Cell Res., 29, 83, 10.1038/s41422-018-0124-5 Kim, 2019, Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation, Nat. Chem. Biol., 15, 907, 10.1038/s41589-019-0344-0 Delandre, 2009, Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects palmitoylation and alters interaction with other proteins at the cell surface, Exp. Cell Res., 315, 1953, 10.1016/j.yexcr.2009.03.013 Dixon, 2021, Managing Diabetic Foot Ulcers: Pharmacotherapy for Wound Healing, Drugs, 81, 29, 10.1007/s40265-020-01415-8 Huang, 2021, Effect of a Novel Macrophage-Regulating Drug on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial, JAMA Netw. Open, 4, 10.1001/jamanetworkopen.2021.22607 Sun, 2020, Metabolomics Signatures in Type 2 Diabetes: A Systematic Review and Integrative Analysis, J. Clin. Endocrinol. Metab., 105, 10.1210/clinem/dgz240 Merino, 2018, Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose, Diabetologia, 61, 1315, 10.1007/s00125-018-4599-x Galderisi, 2018, Metabolomics reveals new metabolic perturbations in children with type 1 diabetes, Pediatr. Diabetes, 19, 59, 10.1111/pedi.12524 Drogan, 2015, Untargeted metabolic profiling identifies altered serum metabolites of type 2 diabetes mellitus in a prospective, nested case control study, Clin. Chem., 61, 487, 10.1373/clinchem.2014.228965 Kong, 2022, Inflammation and atherosclerosis: signaling pathways and therapeutic intervention, Signal Transduct. Target. Ther., 7, 131, 10.1038/s41392-022-00955-7 Dorland, 1993, Phenylpyruvate, fetal damage, and maternal phenylketonuria syndrome, Lancet, 341, 1351, 10.1016/0140-6736(93)90866-F Suzuki, 2021, Energy metabolism profile of the effects of amino acid treatment on hepatocytes: Phenylalanine and phenylpyruvate inhibit glycolysis of hepatocytes, Nutrition, 82, 10.1016/j.nut.2020.111042 Zhang, 2020, Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization, Cell Metab., 31, 1136, 10.1016/j.cmet.2020.05.004 Zhang, 2022, Inhibition of UBA6 by inosine augments tumour immunogenicity and responses, Nat. Commun., 13, 5413, 10.1038/s41467-022-33116-z Chen, 2021, The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity, Cell Metab., 33, 565, 10.1016/j.cmet.2021.02.007 Bellizzi, 2000, The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis, Proc. Natl. Acad. Sci. USA, 97, 4573, 10.1073/pnas.080508097 Zhang, 2021, Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases, Front. Immunol., 12 Lu, 2019, Palmitoylation of NOD1 and NOD2 is required for bacterial sensing, Science, 366, 460, 10.1126/science.aau6391 Zhou, 2023, Protein palmitoylation in cancer: molecular functions and therapeutic potential, Mol. Oncol., 17, 3, 10.1002/1878-0261.13308 Dong, 2023, Palmitoylation couples insulin hypersecretion with beta cell failure in diabetes, Cell Metab., 35, 332, 10.1016/j.cmet.2022.12.012 Wang, 2023, Palmitoylation prevents sustained inflammation by limiting NLRP3 inflammasome activation through chaperone-mediated autophagy, Mol. Cell, 83, 281, 10.1016/j.molcel.2022.12.002 Chen, 2022, CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate, J. Exp. Med., 219, 10.1084/jem.20211314 Shu, 2022, The role of CD36 in cardiovascular disease, Cardiovasc. Res., 118, 115, 10.1093/cvr/cvaa319 Wang, 2019, CD36 tango in cancer: signaling pathways and functions, Theranostics, 9, 4893, 10.7150/thno.36037 Chen, 2019, Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses, Circ. Res., 125, 1087, 10.1161/CIRCRESAHA.119.315833 Geng, 2021, Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory, Front. Pharmacol., 12, 10.3389/fphar.2021.653940 Li, 2018, Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model, Exp. Mol. Med., 50, 1 Lee, 2020, Attack of the NETs! NETosis primes IL-1beta-mediated inflammation in diabetic foot ulcers, Clin. Sci., 134, 1399, 10.1042/CS20200240 Feldmeyer, 2007, The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes, Curr. Biol., 17, 1140, 10.1016/j.cub.2007.05.074 Iglesias-Bartolome, 2018, Transcriptional signature primes human oral mucosa for rapid wound healing, Sci. Transl. Med., 10, 10.1126/scitranslmed.aap8798 Audu, 2022, Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair, Cell. Mol. Immunol., 19, 1251, 10.1038/s41423-022-00919-5 Peng, 2022, A cellular thermal shift assay for detecting amino acid sites involved in drug target engagement, STAR Protoc., 3, 10.1016/j.xpro.2022.101423 van Diggelen, 1999, A rapid fluorogenic palmitoyl-protein thioesterase assay: pre- and postnatal diagnosis of INCL, Mol. Genet. Metab., 66, 240, 10.1006/mgme.1999.2809