Beyond TGFβ1 - novel treatment strategies targeting lung fibrosis

Claudia Sim1, Emma Lamanna1, Frank Cirnigliaro1, Maggie Lam1
1Monash University, Clayton, Melbourne, Australia

Tài liệu tham khảo

Al-Alawi, 2014, Transforming growth factor β and severe asthma: a perfect storm, Respir. Med., 10.1016/j.rmed.2014.08.008 Ameshima, 2003, Peroxisome proliferator-activated receptor gamma (PPARγ) expression is decreased in pulmonary hypertension and affects endothelial cell growth, Circ. Res., 92, 1162, 10.1161/01.RES.0000073585.50092.14 Anderson, 2016, Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial, PLoS One, 11 Aoki, 2009, Pioglitazone, a peroxisome proliferator-activated receptor gamma ligand, suppresses bleomycin-induced acute lung injury and fibrosis, Respiration, 77, 311, 10.1159/000168676 Bagher, 2021, Crosstalk between mast cells and lung fibroblasts is modified by alveolar extracellular matrix and influences epithelial migration, Int. J. Mol. Sci., 22, 1, 10.3390/ijms22020506 Bärnthaler, 2019, Inhibiting eicosanoid degradation exerts antifibrotic effects in a pulmonary fibrosis mouse model and human tissue, J. Allergy Clin. Immunol. Batta, 2020, American Thoracic Society Beck, 2020, Potent and selective human prostaglandin F (FP) receptor antagonist (BAY-6672) for the treatment of idiopathic pulmonary fibrosis (IPF), J. Med. Chem., 63, 11639, 10.1021/acs.jmedchem.0c00834 Behringer, 2016, Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension, Naunyn. Schmiedebergs. Arch. Pharmacol., 389, 369, 10.1007/s00210-015-1205-3 Behr, 2021, Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial, Lancet Respir. Med., 9, 476, 10.1016/S2213-2600(20)30554-3 Benayoun, 2001, Regulation of peroxisome proliferator-activated receptor γ expression in human asthmatic airways: relationship with proliferation, apoptosis, and airway remodeling, Am. J. Respir. Crit. Care Med., 164, 1487, 10.1164/ajrccm.164.8.2101070 Bourke, 2014, Novel small airway bronchodilator responses to rosiglitazone in mouse lung slices, Am. J. Respir. Cell Mol. Biol., 50, 748, 10.1165/rcmb.2013-0247OC Bryant, 2015, Expression of mutant bone morphogenetic protein receptor II worsens pulmonary hypertension secondary to pulmonary fibrosis, Pulm. Circ., 5, 681, 10.1086/683811 Burger, 1995, Evidence that cellular proliferation contributes to relaxin-induced growth of both the vagina and the cervix in the pregnant rat, Endocrinology, 136, 4820, 10.1210/endo.136.11.7588212 Burgess, 2005, PPARγ agonists inhibit TGF-β induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis, Am. J. Physiol. - Lung Cell. Mol. Physiol., 288, 1146, 10.1152/ajplung.00383.2004 Calvier, 2017, PPARγ links BMP2 and TGFβ1 pathways in vascular smooth muscle cells, regulating cell proliferation and glucose metabolism, Cell Metab., 25 Chen, 2020, Nintedanib reduces neutrophil chemotaxis via activating GRK2 in bleomycin-induced pulmonary fibrosis, Int. J. Mol., 21, 4735, 10.3390/ijms21134735 Chen, 2016, Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension, Am. J. Physiol. Lung Cell Mol. Physiol., 311, 238, 10.1152/ajplung.00142.2016 Chow, 2012, Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS, PLoS One, 7, 10.1371/journal.pone.0042714 Conti, 2018, Critical role of inflammatory mast cell in fibrosis: potential therapeutic effect of IL-37, Cell Prolif, 51, 1, 10.1111/cpr.12475 Cortegiani, 2020, Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review, Pulmonology, 27, 52, 10.1016/j.pulmoe.2020.07.003 Dakhlallah, 2013, Epigenetic regulation of mir-17∼92 contributes to the pathogenesis of pulmonary fibrosis, Am. J. Respir. Crit. Care Med., 187, 397, 10.1164/rccm.201205-0888OC Donovan, 2015, Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease, Am. J. Physiol. Lung Cell. Mol. Physiol., 309, L1219, 10.1152/ajplung.00156.2015 Feng, 2016, BMPR2 gene delivery reduces mutation-related PAH and counteracts TGF-β-mediated pulmonary cell signalling, Respirology, 21, 526, 10.1111/resp.12712 Fernandez, 2012, The impact of TGF-β on lung fibrosis: from targeting to biomarkers, Proc. Am. Thorac. Soc., 111, 10.1513/pats.201203-023AW Ferreira-Gomes, 2020, In severe COVID-19, SARS-CoV-2 induces a chronic, TGF-β-dominated adaptive immune response, medRxiv. Gantier, 2020, Animal models of COVID-19 hyper-inflammation, Respirology, 2019, 222 Gosens, 2015, Bronchoconstriction and airway biology: potential impact and therapeutic opportunities, Chest, 147, 798, 10.1378/chest.14-1142 Grainge, 2011, Effect of bronchoconstriction in airway remodeling in asthma. N. Engl. J. Med, 364, 2006 Grimminger, 2015, The role of tyrosine kinases in the pathogenesis of idiopathic pulmonary fibrosis, Eur. Respir. J., 10.1183/09031936.00149614 Groth, 2014, Inflammatory cytokines in pulmonary hypertension, Respir. Res., 15, 47, 10.1186/1465-9921-15-47 Guiot, 2020, Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p, Thorax, 75, 870, 10.1136/thoraxjnl-2019-214077 Guirao, 2020, High serum IL-6 values increase the risk of mortality and the severity of pneumonia in patients diagnosed with COVID-19, Mol. Immunol., 128, 64, 10.1016/j.molimm.2020.10.006 Hansmann, 2020, Activation of the metabolic master regulator PPARg: a potential pioneering therapy for pulmonary arterial hypertension, Am. J. Respir. Cell Mol. Biol., 62, 143, 10.1165/rcmb.2019-0226PS Harper, 2019, BMPR2-expressing bone marrow-derived endothelial-like progenitor cells alleviate pulmonary arterial hypertension in vivo, Respirology, 24, 1095, 10.1111/resp.13552 Harper, 2016, BMPR2 gene therapy for PAH acts via Smad and non-Smad signalling, Respirology, 21, 727, 10.1111/resp.12729 Hirano, 2006, Pirfenidone modulates airway responsiveness, inflammation, and remodeling after repeated challenge, Am. J. Respir. Cell Mol. Biol., 35, 366, 10.1165/rcmb.2005-0452OC Hogan, 2011, Electrophilic PPARγ ligands attenuate IL-1 and silica-induced inflammatory mediator production in human lung fibroblasts via a PPARγ-independent mechanism, PPAR Res., 2011 Honda, 2004, Peroxisome proliferator-activated receptor γ is expressed in airways and inhibits features of airway remodeling in a mouse asthma model, J. Allergy Clin. Immunol., 113, 882, 10.1016/j.jaci.2004.02.036 Hostettler, 2015, Anti-fibrotic effects of pirfenidone in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis, Eur. Respir. J., PA3040 Huang, 2011, Relaxin regulates myofibroblast contractility and protects against lung fibrosis, Am. J. Pathol., 179, 2751, 10.1016/j.ajpath.2011.08.018 Jiang, 2021, Dysregulation of BMP9/BMPR2/SMAD signalling pathway contributes to pulmonary fibrosis and pulmonary hypertension induced by bleomycin in rats, Br. J. Pharmacol., 178, 203, 10.1111/bph.15285 John, 2021, COVID-19 and pulmonary fibrosis: a potential role for lung epithelial cells and fibroblasts, Immunol. Rev., 1 Kadota, 2021, Human bronchial epithelial cell‐derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF‐β‐WNT crosstalk, J. Extracell. Vesicles, 10 Kadota, 2020, Extracellular vesicles from fibroblasts induce epithelial-cell senescence in pulmonary fibrosis, Am. J. Respir. Cell Mol. Biol., 63, 623, 10.1165/rcmb.2020-0002OC Kai, 2020, Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors—lessons from available evidence and insights into COVID-19, Hypertens. Res., 10.1038/s41440-020-0455-8 Kaler, 2017, A randomized, placebo-controlled, double-blinded, crossover trial of pioglitazone for severe asthma, J. Allergy Clin. Immunol., 140, 1716, 10.1016/j.jaci.2017.05.033 Khan, 2017, A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome, Crit. Care, 21, 1, 10.1186/s13054-017-1823-x Khoo, 2020, A randomized, double-blinded, placebo-controlled, dose-escalation Phase 1 study of aerosolized pirfenidone delivered via the PARI Investigational eFlow nebulizer in volunteers and patients with Idiopathic pulmonary fibrosis, J. Aerosol Med. Pulm. Drug Deliv., 33, 15, 10.1089/jamp.2018.1507 King Jr, 2014, A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis, N. Engl. J. Med., 370, 2083, 10.1056/NEJMoa1402582 Kreuter, 2019, Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): Insights from the INPULSIS® trials, Respir. Res., 20, 1, 10.1186/s12931-019-1037-7 Lam, 2016, Serelaxin elicits bronchodilation and enhances β-adrenoceptor-mediated airway relaxation, Front. Pharmacol., 7, 1, 10.3389/fphar.2016.00406 Lam, 2018, Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases, Pharmacol. Ther., 187, 61, 10.1016/j.pharmthera.2018.02.004 Lancaster, 2016, Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: Integrated analysis of cumulative data from 5 clinical trials, BMJ Open Respir. Res., 3, 1, 10.1136/bmjresp-2015-000105 Lazar, 2018, Reversing the curse on PPAR?, J. Clin. Invest, 128, 2202, 10.1172/JCI121392 Lee, 2016, Effect of intranasal rosiglitazone on airway inflammation and remodeling in a murine model of chronic asthma, Korean J. Intern. Med., 31, 89, 10.3904/kjim.2016.31.1.89 Lehmann, 2018, Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis, Respir. Res., 19, 175, 10.1186/s12931-018-0876-y Leslie, 2020, FPR-1 is an important regulator of neutrophil recruitment and a tissue-specific driver of pulmonary fibrosis, JCI Insight, 5, 1, 10.1172/jci.insight.125937 Le, 2014, Blockade of IL-6 trans signaling attenuates pulmonary fibrosis, J. Immunol., 193, 3755, 10.4049/jimmunol.1302470 Liu, 2019, Pirfenidone activates cannabinoid receptor 2 in a mouse model of bleomycin‑induced pulmonary fibrosis, Exp. Ther. Med. McDonald, 2020, Healing after Covid-19: are survivors at risk for pulmonary fibrosis?, Am. J. Physiol. Lung Cell. Mol. Physiol. Mei, 2020, Activation of angiotensin II type-2 receptor protects against cigarette smoke-induced COPD, Pharmacol. Res, 161 Meng, 2015, The angiotensin-converting enzyme 2/angiotensin (1-7)/mas axis protects against lung fibroblast migration and lung fibrosis by inhibiting the NOX4-derived ROS-mediated RhoA/Rho kinase pathway, Antioxidants Redox Signal, 22, 241, 10.1089/ars.2013.5818 Milam, 2008, PPAR-γ agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis, Am. J. Physiol. Lung Cell. Mol. Physiol., 294, L891, 10.1152/ajplung.00333.2007 Monteil, 2020, Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2, Cell, 181 Nathan, 2019, Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment, Respir. Med., 153, 44, 10.1016/j.rmed.2019.04.016 NCT04452435, 2020. Safety and Efficacy of C21 in Subjects With COVID-19. 〈https://clinicaltrials.gov/show/NCT04452435〉. Nisbet, 2010, Rosiglitazone attenuates chronic hypoxia-induced pulmonary hypertension in a mouse model, Am. J. Respir. Cell Mol. Biol., 42, 482, 10.1165/rcmb.2008-0132OC Ni, 2020, Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19, Crit. Care, 24 Noble, 2011, Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials, Lancet, 377, 1760, 10.1016/S0140-6736(11)60405-4 Overed-Sayer, 2020, Inhibition of mast cells: a novel mechanism by which nintedanib may elicit anti-fibrotic effects, Thorax, 75, 754, 10.1136/thoraxjnl-2019-214000 Pan, 2021, Artesunate ameliorates cigarette smoke-induced airway remodelling via PPAR-γ/TGF-β1/Smad2/3 signalling pathway, Respir. Res., 22, 1, 10.1186/s12931-021-01687-y Papiris, 2018, High levels of IL-6 and IL-8 characterize early-on idiopathic pulmonary fibrosis acute exacerbations, Cytokine, 102, 168, 10.1016/j.cyto.2017.08.019 Patel, 2003, Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for Chronic obstructive pulmonary disease therapy, J. Immunol., 170, 2663, 10.4049/jimmunol.170.5.2663 Patel, 2019, Role of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in airway reactivity and inflammation in an allergic mouse model of asthma, Immunopharmacol. Immunotoxicol., 41, 428, 10.1080/08923973.2019.1609026 Pini, 2016, Protection from cigarette smoke-induced vascular injury by recombinant human relaxin-2 (serelaxin), J. Cell. Mol. Med., 20, 891, 10.1111/jcmm.12802 Pini, 2016, Protection from cigarette smoke-induced lung dysfunction and damage by H2 relaxin (Serelaxin), J. Pharmacol. Exp. Ther., 357, 451, 10.1124/jpet.116.232215 Pini, 2010, Prevention of bleomycin-induced pulmonary fibrosis by a novel antifibrotic peptide with relaxin-like activity, J. Pharmacol. Exp. Ther., 335, 589, 10.1124/jpet.110.170977 Prosseda, 2021, Novel advances in modifying BMPR2 signaling in PAH, Genes ((Basel)), 12, 1 Ranchoux, 2015, Endothelial-to-mesenchymal transition in pulmonary hypertension, Circulation, 131, 1006, 10.1161/CIRCULATIONAHA.114.008750 Rathinasabapathy, 2018, The selective angiotensin II type 2 receptor agonist, compound 21, attenuates the progression of lung fibrosis and pulmonary hypertension in an experimental model of bleomycin-induced lung injury, Front. Physiol., 9, 1, 10.3389/fphys.2018.00180 Reddy, 2014, Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages, FASEB J., 28, 5299, 10.1096/fj.14-256263 Reynolds, 2012, Targeted gene delivery of BMPR2 attenuates pulmonary hypertension, Eur. Respir. J., 39, 329, 10.1183/09031936.00187310 Reynolds, 2007, Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension, Am. J. Physiol. - Lung Cell. Mol. Physiol., 292, 1182, 10.1152/ajplung.00020.2006 Richeldi, 2011, Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis, N. Engl. J. Med., 365, 1079, 10.1056/NEJMoa1103690 Richeldi, 2014, Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis, N. Engl. J. Med., 370, 2071, 10.1056/NEJMoa1402584 Rol, 2018, TGF-β and BMPR2 signaling in PAH: two black sheep in one family, Int. J. Mol. Sci, 10.3390/ijms19092585 Royce, 2014, Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease, Clin. Exp. Allergy, 44, 1399, 10.1111/cea.12391 Shi, 2020, Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study, Lancet Infect. Dis., 20, 425, 10.1016/S1473-3099(20)30086-4 Soon, 2015, Bone morphogenetic protein receptor type II deficiency and increased inflammatory cytokine production: a gateway to pulmonary arterial hypertension, Am. J. Respir. Crit. Care Med., 192, 859, 10.1164/rccm.201408-1509OC Spiekerkoetter, 2017, Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension, Eur. Respir. J., 50, 1, 10.1183/13993003.02449-2016 Spiekerkoetter, 2013, FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension, J. Clin. Invest., 123, 3600, 10.1172/JCI65592 Star, 2013, ALK2 and BMPR2 knockdown and endothelin-1 production by pulmonary microvascular endothelial cells, Microvasc. Res., 85, 46, 10.1016/j.mvr.2012.10.012 Steiner, 2009, Interleukin-6 overexpression induces pulmonary hypertension, Circ. Res., 104, 236, 10.1161/CIRCRESAHA.108.182014 Takahashi, 2006, Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension, Am. J. Physiol. - Lung Cell. Mol. Physiol., 290, L450, 10.1152/ajplung.00206.2005 Tan, 2016, Expression of RXFP1 is decreased in idiopathic pulmonary fibrosis: implications for relaxin-based therapies, Am. J. Respir. Crit. Care Med., 194, 1392, 10.1164/rccm.201509-1865OC Teerlink, 2013, Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial, Lancet, 381, 29, 10.1016/S0140-6736(12)61855-8 Teerlink, 2017, Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study, Eur. J. Heart Fail., 19, 800, 10.1002/ejhf.830 Unemori, 1996, Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo, J. Clin. Invest., 98, 2739, 10.1172/JCI119099 Wang, 2015, Angiotensin-converting enzyme 2 attenuates bleomycin-induced lung fibrosis in mice, Cell. Physiol. Biochem., 36, 697, 10.1159/000430131 Ward, 2004, PPAR gamma ligands, 15-deoxy-delta12,14-prostaglandin J2 and rosiglitazone regulate human cultured airway smooth muscle proliferation through different mechanisms, Br. J. Pharmacol, 141, 517, 10.1038/sj.bjp.0705630 Wei, 2021, Blocking LOXL2 and TGF β 1 signalling induces collagen I turnover in precision- ­ cut lung slices derived from patients with idiopathic pulmonary fibrosis, Thorax, 0, 1 Wei, 2021, Inhibition of DNA methylation derepresses PPARγ and attenuates pulmonary fibrosis, Br. J. Pharmacol., 0 Winkler, 2020, SARS-CoV-2 infection of hACE2 transgenic mice causes severe lung inflammation and impaired function, Nat. Immunol., 21, 1327, 10.1038/s41590-020-0778-2 Wollin, 2014, Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis, J. Pharmacol. Exp. Ther., 349, 209, 10.1124/jpet.113.208223 Wollin, 2015, Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis, Eur. Respir. J., 10.1183/09031936.00174914 Yang, 2009, Angiotensin II induces connective tissue growth factor and collagen i expression via transforming growth factor-β-dependent and -independent Smad pathways: the role of Smad3, Hypertension, 54, 877, 10.1161/HYPERTENSIONAHA.109.136531 Zoufaly, 2020, Human recombinant soluble ACE2 in severe COVID-19, Lancet Respir. Med., 8, 1154, 10.1016/S2213-2600(20)30418-5