{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:29:24Z","timestamp":1794022164696,"version":"4.8.0"},"reference-count":110,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Systemic sclerosis (SSc) is a disease of connective tissue with high rate of morbidity and mortality\u00a0highlighted by extreme fibrosis affecting various organs such as the dermis, lungs,  and\u00a0heart. Until now, there is no specific cure for the\u00a0fibrosis occurred\u00a0in SSc\u00a0disease. The SSc pathogenesis is yet unknown, but transforming growth factor beta (TGF-\u03b2), endothelin-1 (ET-1), and Ras-ERK1\/2 cascade are the main factors contributing\u00a0to the\u00a0tissue fibrosis through extracellular matrix (ECM) accumulation. Several studies have hallmarked the association of ET-1 with or without TGF-\u03b2 and Ras-ERK1\/2 signaling in the development of SSc disease, vasculopathy, and fibrosis of the dermis, lungs, and several organs. Accordingly, different\u00a0clinical and experimental studies have indicated the potential therapeutic role of ET-1 and Ras antagonists in these situations in SSc. In addition, ET-1 and connective tissue growth factor (CTGF) as a cofactor of the TGF-\u03b2 cascade play a substantial initiative role in inducing fibrosis. Once initiated, TGF-\u03b2 alone or in combination with ET-1 and CTGF can activate several kinase proteins such as the Ras-ERK1\/2 pathway that serve\u00a0as the fundamental factor for developing fibrosis. Furthermore, Salirasib is a synthetic small molecule that is able to inhibit all Ras forms. Therefore, it can be used as a potent therapeutic factor for fibrotic disorders. So, this review discusses  the role of TGF-\u03b2\/ET-1\/Ras signaling and their involvement in SSc pathogenesis, particularly in its fibrotic situation.<\/jats:p>","DOI":"10.1186\/s13075-022-02787-w","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T07:03:16Z","timestamp":1652425396000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The role of endothelin and RAS\/ERK signaling in immunopathogenesis-related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications"],"prefix":"10.1186","volume":"24","author":[{"given":"Mohsen","family":"Rokni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Sadeghi Shaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda","family":"Kavosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Shokoofi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Mahmoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Farhadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"issue":"10","key":"2787_CR1","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/s41584-021-00683-2","volume":"17","author":"P-S Tsou","year":"2021","unstructured":"Tsou P-S, Varga J, O\u2019Reilly S. Advances in epigenetics in systemic sclerosis: molecular mechanisms and therapeutic potential. Nat Rev Rheumatol. 2021;17(10):596\u2013607.","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"2787_CR2","doi-asserted-by":"publisher","first-page":"102730","DOI":"10.1016\/j.autrev.2020.102730","volume":"20","author":"C Varrica","year":"2021","unstructured":"Varrica C, Dias HS, Reis C, Carvalheiro M, Sim\u00f5es S. Targeted delivery in scleroderma fibrosis. Autoimmun Rev. 2021;20(2):102730.","journal-title":"Autoimmun Rev"},{"issue":"3","key":"2787_CR3","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1111\/cei.13238","volume":"195","author":"M Brown","year":"2019","unstructured":"Brown M, O'Reilly S. The immunopathogenesis of fibrosis in systemic sclerosis. Clin Exp Immunol. 2019;195(3):310\u201321.","journal-title":"Clin Exp Immunol"},{"issue":"9","key":"2787_CR4","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1093\/rheumatology\/kes090","volume":"51","author":"S O\u2019Reilly","year":"2012","unstructured":"O\u2019Reilly S, H\u00fcgle T, Van Laar JM. T cells in systemic sclerosis: a reappraisal. Rheumatology. 2012;51(9):1540\u20139.","journal-title":"Rheumatology."},{"issue":"8","key":"2787_CR5","doi-asserted-by":"publisher","first-page":"102583","DOI":"10.1016\/j.autrev.2020.102583","volume":"19","author":"M Mahler","year":"2020","unstructured":"Mahler M, Hudson M, Bentow C, Roup F, Beretta L, Pilar Sime\u00f3n C, et al. Autoantibodies to stratify systemic sclerosis patients into clinically actionable subsets. Autoimmun Rev. 2020;19(8):102583.","journal-title":"Autoimmun Rev"},{"issue":"1","key":"2787_CR6","doi-asserted-by":"publisher","first-page":"R10","DOI":"10.1186\/ar1860","volume":"8","author":"C Chizzolini","year":"2006","unstructured":"Chizzolini C, Parel Y, Scheja A, Dayer JM. Polarized subsets of human T-helper cells induce distinct patterns of chemokine production by normal and systemic sclerosis dermal fibroblasts. Arthritis Res Ther. 2006;8(1):R10.","journal-title":"Arthritis Res Ther"},{"issue":"24","key":"2787_CR7","doi-asserted-by":"publisher","first-page":"6297","DOI":"10.1111\/j.1742-4658.2005.05016.x","volume":"272","author":"A Horstmeyer","year":"2005","unstructured":"Horstmeyer A, Licht C, Scherr G, Eckes B, Krieg T. Signalling and regulation of collagen I synthesis by ET-1 and TGF-beta1. FEBS J. 2005;272(24):6297\u2013309.","journal-title":"FEBS J"},{"issue":"Suppl 2","key":"2787_CR8","first-page":"140","volume":"76","author":"S Soldano","year":"2017","unstructured":"Soldano S, Montagna P, Brizzolara R, Trombetta A, Sulli A, Pizzorni C, et al. OP0212\u00a0Endothelin-1 induces a profibrotic phenotype in cultured human microvascular endothelial and circulating monocyte\/macrophage cells. Ann Rheum Dis. 2017;76(Suppl 2):140.","journal-title":"Ann Rheum Dis"},{"issue":"suppl_3","key":"2787_CR9","doi-asserted-by":"publisher","first-page":"iii3","DOI":"10.1093\/rheumatology\/ken481","volume":"48","author":"DJ Abraham","year":"2009","unstructured":"Abraham DJ, Krieg T, Distler J, Distler O. Overview of pathogenesis of systemic sclerosis. Rheumatology. 2009;48(suppl_3):iii3\u20137.","journal-title":"Rheumatology."},{"key":"2787_CR10","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.3389\/fphys.2018.01177","volume":"9","author":"AE Abdulle","year":"2018","unstructured":"Abdulle AE, Diercks GFH, Feelisch M, Mulder DJ, van Goor H. The role of oxidative stress in the development of systemic sclerosis related vasculopathy. Front Physiol. 2018;9:1177.","journal-title":"Front Physiol"},{"issue":"5","key":"2787_CR11","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.autrev.2010.09.016","volume":"10","author":"C Chizzolini","year":"2011","unstructured":"Chizzolini C, Brembilla NC, Montanari E, Truchetet ME. Fibrosis and immune dysregulation in systemic sclerosis. Autoimmun Rev. 2011;10(5):276\u201381.","journal-title":"Autoimmun Rev"},{"issue":"6","key":"2787_CR12","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1097\/BOR.0000000000000543","volume":"30","author":"DA Gyftaki-Venieri","year":"2018","unstructured":"Gyftaki-Venieri DA, Abraham DJ, Ponticos M. Insights into myofibroblasts and their activation in scleroderma: opportunities for therapy? Curr Opin Rheumatol. 2018;30(6):581\u20137.","journal-title":"Curr Opin Rheumatol"},{"issue":"10","key":"2787_CR13","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1136\/annrheumdis-2013-203535","volume":"73","author":"B Maurer","year":"2014","unstructured":"Maurer B, Distler A, Suliman YA, Gay RE, Michel BA, Gay S, et al. Vascular endothelial growth factor aggravates fibrosis and vasculopathy in experimental models of systemic sclerosis. Ann Rheum Dis. 2014;73(10):1880\u20137.","journal-title":"Ann Rheum Dis"},{"key":"2787_CR14","doi-asserted-by":"crossref","unstructured":"Yang F, Bai X, Dai X, Li Y. The biological processes during wound healing.\u00a0Regen Med.\u00a02021;16(4):373\u201390.","DOI":"10.2217\/rme-2020-0066"},{"key":"2787_CR15","first-page":"105","volume":"4","author":"D Pattanaik","year":"2011","unstructured":"Pattanaik D, Brown M, Postlethwaite AE. Vascular involvement in systemic sclerosis (scleroderma). J Inflamm Res. 2011;4:105\u201325.","journal-title":"J Inflamm Res"},{"issue":"3 Suppl 33","key":"2787_CR16","first-page":"S19","volume":"22","author":"MB Kahaleh","year":"2004","unstructured":"Kahaleh MB. Vascular involvement in systemic sclerosis (SSc). Clin Exp Rheumatol. 2004;22(3 Suppl 33):S19\u201323.","journal-title":"Clin Exp Rheumatol"},{"key":"2787_CR17","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.3389\/fimmu.2018.02383","volume":"9","author":"Y Long","year":"2018","unstructured":"Long Y, Chen W, Du Q, Zuo X, Zhu H. Ubiquitination in scleroderma fibrosis and its treatment. Front Immunol. 2018;9:2383.","journal-title":"Front Immunol"},{"issue":"8","key":"2787_CR18","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/j.cellsig.2008.01.006","volume":"20","author":"A Leask","year":"2008","unstructured":"Leask A. Targeting the TGFbeta, endothelin-1 and CCN2 axis to combat fibrosis in scleroderma. Cell Signal. 2008;20(8):1409\u201314.","journal-title":"Cell Signal"},{"issue":"2_suppl","key":"2787_CR19","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.5301\/jsrd.5000258","volume":"2","author":"Y Kawaguchi","year":"2017","unstructured":"Kawaguchi Y. Contribution of interleukin-6 to the pathogenesis of systemic sclerosis. J Scleroderma Relat Disord. 2017;2(2_suppl):S6\u2013S12.","journal-title":"J Scleroderma Relat Disord"},{"issue":"6","key":"2787_CR20","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1091\/mbc.e03-12-0902","volume":"15","author":"X Shi-Wen","year":"2004","unstructured":"Shi-Wen X, Chen Y, Denton CP, Eastwood M, Renzoni EA, Bou-Gharios G, et al. Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac\/phosphoinositide 3-kinase\/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol Biol Cell. 2004;15(6):2707\u201319.","journal-title":"Mol Biol Cell"},{"key":"2787_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102526","volume":"113","author":"JC Worrell","year":"2020","unstructured":"Worrell JC, O'Reilly S. Bi-directional communication: conversations between fibroblasts and immune cells in systemic sclerosis. J Autoimmun. 2020;113:102526.","journal-title":"J Autoimmun"},{"issue":"2","key":"2787_CR22","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.lfs.2013.12.024","volume":"118","author":"F Rodr\u00edguez-Pascual","year":"2014","unstructured":"Rodr\u00edguez-Pascual F, Busnadiego O, Gonz\u00e1lez-Santamar\u00eda J. The profibrotic role of endothelin-1: is the door still open for the treatment of fibrotic diseases? Life Sci. 2014;118(2):156\u201364.","journal-title":"Life Sci"},{"key":"2787_CR23","doi-asserted-by":"publisher","first-page":"4569826","DOI":"10.1155\/2019\/4569826","volume":"2019","author":"A Sierra-Sep\u00falveda","year":"2019","unstructured":"Sierra-Sep\u00falveda A, Esquinca-Gonz\u00e1lez A, Benavides-Su\u00e1rez SA, Sordo-Lima DE, Caballero-Islas AE, Cabral-Casta\u00f1eda AR, et al. Systemic sclerosis pathogenesis and emerging therapies, beyond the fibroblast. Biomed Res Int. 2019;2019:4569826.","journal-title":"Biomed Res Int"},{"issue":"4","key":"2787_CR24","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.joca.2014.11.002","volume":"23","author":"A Sin","year":"2015","unstructured":"Sin A, Tang W, Wen CY, Chung SK, Chiu KY. The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis. Osteoarthr Cartil. 2015;23(4):516\u201324.","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"2787_CR25","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1124\/pr.115.011833","volume":"68","author":"AP Davenport","year":"2016","unstructured":"Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, et al. Endothelin. Pharmacol Rev. 2016;68(2):357\u2013418.","journal-title":"Pharmacol Rev"},{"issue":"9","key":"2787_CR26","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nrc3546","volume":"13","author":"L Rosan\u00f2","year":"2013","unstructured":"Rosan\u00f2 L, Spinella F, Bagnato A. Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2013;13(9):637\u201351.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"2787_CR27","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13046-016-0401-4","volume":"35","author":"L Rosan\u00f2","year":"2016","unstructured":"Rosan\u00f2 L, Bagnato A. \u03b2-arrestin1 at the cross-road of endothelin-1 signaling in cancer. J Exp Clin Cancer Res. 2016;35(1):121.","journal-title":"J Exp Clin Cancer Res"},{"issue":"3","key":"2787_CR28","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1080\/19768354.2019.1595141","volume":"23","author":"TJ Cho","year":"2019","unstructured":"Cho TJ, Kim HJ, Cho J. Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis. Anim Cells Syst. 2019;23(3):170\u20135.","journal-title":"Anim Cells Syst"},{"issue":"16","key":"2787_CR29","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1177\/1535370220949148","volume":"245","author":"D Ezhilarasan","year":"2020","unstructured":"Ezhilarasan D. Endothelin-1 in portal hypertension: the intricate role of hepatic stellate cells. Exp Biol Med (Maywood). 2020;245(16):1504\u201312.","journal-title":"Exp Biol Med (Maywood)"},{"issue":"9","key":"2787_CR30","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1136\/annrheumdis-2016-210792","volume":"76","author":"E Planas-Rigol","year":"2017","unstructured":"Planas-Rigol E, Terrades-Garcia N, Corbera-Bellalta M, Lozano E, Alba MA, Segarra M, et al. Endothelin-1 promotes vascular smooth muscle cell migration across the artery wall: a mechanism contributing to vascular remodelling and intimal hyperplasia in giant-cell arteritis. Ann Rheum Dis. 2017;76(9):1624\u201334.","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"2787_CR31","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1007\/s00296-017-3797-z","volume":"37","author":"M Hajialilo","year":"2017","unstructured":"Hajialilo M, Noorabadi P, Tekantapeh ST, Mahdavi AM. Endothelin-1, \u03b1-Klotho, 25 (OH) Vit D levels and severity of disease in scleroderma patients. Rheumatol Int. 2017;37(10):1651\u20137.","journal-title":"Rheumatol Int"},{"issue":"2","key":"2787_CR32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3233\/CH-150044","volume":"66","author":"I Silva","year":"2017","unstructured":"Silva I, Teixeira A, Oliveira J, Almeida R, Vasconcelos C. Endothelial dysfunction, microvascular damage and ischemic peripheral vasculopathy in systemic sclerosis. Clin Hemorheol Microcirc. 2017;66(2):117\u201330.","journal-title":"Clin Hemorheol Microcirc"},{"issue":"3","key":"2787_CR33","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s10067-009-1288-7","volume":"29","author":"HS Kim","year":"2010","unstructured":"Kim HS, Park MK, Kim HY, Park SH. Capillary dimension measured by computer-based digitalized image correlated with plasma endothelin-1 levels in patients with systemic sclerosis. Clin Rheumatol. 2010;29(3):247\u201354.","journal-title":"Clin Rheumatol"},{"issue":"1","key":"2787_CR34","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13075-016-1011-4","volume":"18","author":"K Akashi","year":"2016","unstructured":"Akashi K, Saegusa J, Sendo S, Nishimura K, Okano T, Yagi K, et al. Knockout of endothelin type B receptor signaling attenuates bleomycin-induced skin sclerosis in mice. Arthritis Res Ther. 2016;18(1):113.","journal-title":"Arthritis Res Ther"},{"issue":"6473","key":"2787_CR35","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/368693a0","volume":"368","author":"PM Vanhoutte","year":"1994","unstructured":"Vanhoutte PM. Endothelin-1. A matter of life and breath. Nature. 1994;368(6473):693\u20134.","journal-title":"Nature."},{"issue":"11","key":"2787_CR36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026994","volume":"6","author":"JW Leung","year":"2011","unstructured":"Leung JW, Wong WT, Koon HW, Mo FM, Tam S, Huang Y, et al. Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. PLoS One. 2011;6(11):e26994.","journal-title":"PLoS One"},{"issue":"35","key":"2787_CR37","doi-asserted-by":"publisher","first-page":"30444","DOI":"10.1074\/jbc.M111.263657","volume":"286","author":"D Alvarez","year":"2011","unstructured":"Alvarez D, Briassouli P, Clancy RM, Zavadil J, Reed JH, Abellar RG, et al. A novel role of endothelin-1 in linking Toll-like receptor 7-mediated inflammation to fibrosis in congenital heart block. J Biol Chem. 2011;286(35):30444\u201354.","journal-title":"J Biol Chem"},{"issue":"12","key":"2787_CR38","doi-asserted-by":"publisher","first-page":"3340","DOI":"10.1002\/jcp.22690","volume":"226","author":"E Morris","year":"2011","unstructured":"Morris E, Chrobak I, Bujor A, Hant F, Mummery C, Ten Dijke P, et al. Endoglin promotes TGF-\u03b2\/Smad1 signaling in scleroderma fibroblasts. J Cell Physiol. 2011;226(12):3340\u20138.","journal-title":"J Cell Physiol"},{"issue":"3","key":"2787_CR39","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1046\/j.1523-1747.2001.01256.x","volume":"116","author":"X Shi-Wen","year":"2001","unstructured":"Shi-Wen X, Denton CP, Dashwood MR, Holmes AM, Bou-Gharios G, Pearson JD, et al. Fibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1. J Invest Dermatol. 2001;116(3):417\u201325.","journal-title":"J Invest Dermatol"},{"issue":"4","key":"2787_CR40","doi-asserted-by":"publisher","first-page":"H2072","DOI":"10.1152\/ajpheart.01097.2006","volume":"293","author":"A Bouallegue","year":"2007","unstructured":"Bouallegue A, Daou GB, Srivastava AK. Nitric oxide attenuates endothelin-1-induced activation of ERK1\/2, PKB, and Pyk2 in vascular smooth muscle cells by a cGMP-dependent pathway. Am J Physiol Heart Circ Physiol. 2007;293(4):H2072\u20139.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2787_CR41","first-page":"115","volume":"1","author":"A Leask","year":"2009","unstructured":"Leask A. Signaling in fibrosis: targeting the TGF beta, endothelin-1 and CCN2 axis in scleroderma. Front Biosci (Elite Ed). 2009;1:115\u201322.","journal-title":"Front Biosci (Elite Ed)"},{"issue":"6","key":"2787_CR42","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1136\/annrheumdis-2018-214778","volume":"78","author":"SJ Moon","year":"2019","unstructured":"Moon SJ, Bae JM, Park KS, Tagkopoulos I, Kim KJ. Compendium of skin molecular signatures identifies key pathological features associated with fibrosis in systemic sclerosis. Ann Rheum Dis. 2019;78(6):817\u201325.","journal-title":"Ann Rheum Dis"},{"issue":"11","key":"2787_CR43","doi-asserted-by":"publisher","first-page":"6568","DOI":"10.4049\/jimmunol.1003756","volume":"186","author":"K Kambas","year":"2011","unstructured":"Kambas K, Chrysanthopoulou A, Kourtzelis I, Skordala M, Mitroulis I, Rafail S, et al. Endothelin-1 signaling promotes fibrosis in vitro in a bronchopulmonary dysplasia model by activating the extrinsic coagulation cascade. J Immunol. 2011;186(11):6568\u201375.","journal-title":"J Immunol"},{"issue":"14","key":"2787_CR44","doi-asserted-by":"publisher","first-page":"5518","DOI":"10.1128\/MCB.00625-06","volume":"26","author":"X Shi-Wen","year":"2006","unstructured":"Shi-Wen X, Rodr\u00edguez-Pascual F, Lamas S, Holmes A, Howat S, Pearson JD, et al. Constitutive ALK5-independent c-Jun N-terminal kinase activation contributes to endothelin-1 overexpression in pulmonary fibrosis: evidence of an autocrine endothelin loop operating through the endothelin A and B receptors. Mol Cell Biol. 2006;26(14):5518\u201327.","journal-title":"Mol Cell Biol"},{"issue":"1","key":"2787_CR45","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/cr.2008.326","volume":"19","author":"M-J Goumans","year":"2009","unstructured":"Goumans M-J, Liu Z, ten Dijke P. TGF-\u03b2 signaling in vascular biology and dysfunction. Cell Res. 2009;19(1):116\u201327.","journal-title":"Cell Res"},{"issue":"1","key":"2787_CR46","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/cr.2008.326","volume":"19","author":"MJ Goumans","year":"2009","unstructured":"Goumans MJ, Liu Z, ten Dijke P. TGF-beta signaling in vascular biology and dysfunction. Cell Res. 2009;19(1):116\u201327.","journal-title":"Cell Res"},{"issue":"Pt 7","key":"2787_CR47","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1242\/jcs.03419","volume":"120","author":"C Casta\u00f1ares","year":"2007","unstructured":"Casta\u00f1ares C, Redondo-Horcajo M, Mag\u00e1n-Marchal N, ten Dijke P, Lamas S, Rodr\u00edguez-Pascual F. Signaling by ALK5 mediates TGF-beta-induced ET-1 expression in endothelial cells: a role for migration and proliferation. J Cell Sci. 2007;120(Pt 7):1256\u201366.","journal-title":"J Cell Sci"},{"issue":"Suppl 1","key":"2787_CR48","doi-asserted-by":"publisher","first-page":"S39","DOI":"10.1097\/01.fjc.0000166216.27544.22","volume":"44","author":"F Rodr\u00edguez-Pascual","year":"2004","unstructured":"Rodr\u00edguez-Pascual F, Reimunde FM, Redondo-Horcajo M, Lamas S. Transforming growth factor-beta induces endothelin-1 expression through activation of the Smad signaling pathway. J Cardiovasc Pharmacol. 2004;44(Suppl 1):S39\u201342.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"1","key":"2787_CR49","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1684\/ecn.2015.0360","volume":"26","author":"J Jing","year":"2015","unstructured":"Jing J, Dou TT, Yang JQ, Chen XB, Cao HL, Min M, et al. Role of endothelin-1 in the skin fibrosis of systemic sclerosis. Eur Cytokine Netw. 2015;26(1):10\u20134.","journal-title":"Eur Cytokine Netw"},{"issue":"3","key":"2787_CR50","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1002\/art.27307","volume":"62","author":"D Lagares","year":"2010","unstructured":"Lagares D, Garc\u00eda-Fern\u00e1ndez RA, Jim\u00e9nez CL, Mag\u00e1n-Marchal N, Busnadiego O, Lamas S, et al. Endothelin 1 contributes to the effect of transforming growth factor beta1 on wound repair and skin fibrosis. Arthritis Rheum. 2010;62(3):878\u201389.","journal-title":"Arthritis Rheum"},{"issue":"7547","key":"2787_CR51","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/520278a","volume":"520","author":"LH Cancer","year":"2015","unstructured":"Cancer LH. The Ras renaissance. Nature. 2015;520(7547):278\u201380.","journal-title":"Nature."},{"issue":"1","key":"2787_CR52","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","volume":"170","author":"DK Simanshu","year":"2017","unstructured":"Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170(1):17\u201333.","journal-title":"Cell."},{"issue":"4","key":"2787_CR53","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1158\/1535-7163.MCT-19-0660","volume":"19","author":"L Shu","year":"2020","unstructured":"Shu L, Wang D, Saba NF, Chen ZG. A historic perspective and overview of H-Ras structure, oncogenicity, and targeting. Mol Cancer Ther. 2020;19(4):999\u20131007.","journal-title":"Mol Cancer Ther"},{"key":"2787_CR54","unstructured":"Matallanas D, Crespo P. New druggable targets in the Ras pathway? Current opinion in molecular therapeutics. 2010;12(6):674\u201383."},{"issue":"1","key":"2787_CR55","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrc969","volume":"3","author":"J Downward","year":"2003","unstructured":"Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3(1):11\u201322.","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"2787_CR56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018049","volume":"6","author":"Y Nevo","year":"2011","unstructured":"Nevo Y, Aga-Mizrachi S, Elmakayes E, Yanay N, Ettinger K, Elbaz M, et al. The Ras antagonist, farnesylthiosalicylic acid (FTS), decreases fibrosis and improves muscle strength in dy\/dy mouse model of muscular dystrophy. PLoS One. 2011;6(3):e18049.","journal-title":"PLoS One"},{"issue":"4","key":"2787_CR57","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/sj.leu.2401367","volume":"13","author":"S Weijzen","year":"1999","unstructured":"Weijzen S, Velders MP, Kast WM. Modulation of the immune response and tumor growth by activated Ras. Leukemia. 1999;13(4):502\u201313.","journal-title":"Leukemia."},{"issue":"1-2","key":"2787_CR58","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jneuroim.2005.07.008","volume":"168","author":"M Kafri","year":"2005","unstructured":"Kafri M, Kloog Y, Korczyn AD, Ferdman-Aronovich R, Drory V, Katzav A, et al. Inhibition of Ras attenuates the course of experimental autoimmune neuritis. J Neuroimmunol. 2005;168(1-2):46\u201355.","journal-title":"J Neuroimmunol"},{"issue":"4","key":"2787_CR59","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1097\/01.ASN.0000057543.55318.8B","volume":"14","author":"HC Clarke","year":"2003","unstructured":"Clarke HC, Kocher HM, Khwaja A, Kloog Y, Cook HT, Hendry BM. Ras antagonist farnesylthiosalicylic acid (FTS) reduces glomerular cellular proliferation and macrophage number in rat thy-1 nephritis. J Am Soc Nephrol. 2003;14(4):848\u201354.","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"2787_CR60","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1046\/j.1365-2249.2001.01674.x","volume":"126","author":"A Katzav","year":"2001","unstructured":"Katzav A, Kloog Y, Korczyn AD, Niv H, Karussis DM, Wang N, et al. Treatment of MRL\/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS). Clin Exp Immunol. 2001;126(3):570\u20137.","journal-title":"Clin Exp Immunol"},{"issue":"6","key":"2787_CR61","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/ki.2009.498","volume":"77","author":"MT Grande","year":"2010","unstructured":"Grande MT, Fuentes-Calvo I, Ar\u00e9valo M, Heredia F, Santos E, Mart\u00ednez-Salgado C, et al. Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following ureteral obstruction in mice. Kidney Int. 2010;77(6):509\u201318.","journal-title":"Kidney Int"},{"issue":"2","key":"2787_CR62","first-page":"725","volume":"53","author":"S Sugita","year":"2018","unstructured":"Sugita S, Enokida H, Yoshino H, Miyamoto K, Yonemori M, Sakaguchi T, et al. HRAS as a potential therapeutic target of salirasib RAS inhibitor in bladder cancer. Int J Oncol. 2018;53(2):725\u201336.","journal-title":"Int J Oncol"},{"issue":"10","key":"2787_CR63","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1007\/s10620-014-3207-2","volume":"59","author":"R Neeman","year":"2014","unstructured":"Neeman R, Abramovitch S, Sharvit E, Elad-Sfadia G, Haklai R, Kloog Y, et al. Vitamin D and S-farnesylthiosalicylic acid have a synergistic effect on hepatic stellate cells proliferation. Dig Dis Sci. 2014;59(10):2462\u20139.","journal-title":"Dig Dis Sci"},{"issue":"4","key":"2787_CR64","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.4049\/jimmunol.165.4.2149","volume":"165","author":"H Ihn","year":"2000","unstructured":"Ihn H, Tamaki K. Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway. J Immunol. 2000;165(4):2149\u201355.","journal-title":"J Immunol"},{"issue":"6","key":"2787_CR65","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.3892\/ijmm.2016.2767","volume":"38","author":"ER Simo-Cheyou","year":"2016","unstructured":"Simo-Cheyou ER, Vardatsikos G, Srivastava AK. Src tyrosine kinase mediates endothelin-1-induced early growth response protein-1 expression via MAP kinase-dependent pathways in vascular smooth muscle cells. Int J Mol Med. 2016;38(6):1879\u201386.","journal-title":"Int J Mol Med"},{"issue":"9","key":"2787_CR66","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1161\/ATVBAHA.107.146746","volume":"27","author":"A Yogi","year":"2007","unstructured":"Yogi A, Callera GE, Montezano AC, Aranha AB, Tostes RC, Schiffrin EL, et al. Endothelin-1, but not Ang II, activates MAP kinases through c-Src independent Ras-Raf dependent pathways in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2007;27(9):1960\u20137.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"2","key":"2787_CR67","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S0022-4804(03)00213-0","volume":"115","author":"Y Wada","year":"2003","unstructured":"Wada Y, Fujimori M, Suzuki J, Tsukioka K, Ito K, Sawa Y, et al. Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen. J Surg Res. 2003;115(2):294\u2013302.","journal-title":"J Surg Res"},{"key":"2787_CR68","doi-asserted-by":"crossref","unstructured":"Seo HY, Lee SH, Lee JH, Kang YN, Hwang JS, Park KG, et al. Src inhibition attenuates liver fibrosis by preventing hepatic stellate cell activation and decreasing connetive tissue growth factor. Cells. 2020;9(3):558.","DOI":"10.3390\/cells9030558"},{"issue":"8","key":"2787_CR69","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1021\/cb300172e","volume":"7","author":"KR Brandvold","year":"2012","unstructured":"Brandvold KR, Steffey ME, Fox CC, Soellner MB. Development of a highly selective c-Src kinase inhibitor. ACS Chem Biol. 2012;7(8):1393\u20138.","journal-title":"ACS Chem Biol"},{"issue":"4","key":"2787_CR70","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/wrr.12889","volume":"29","author":"A Leask","year":"2021","unstructured":"Leask A. The hard problem: mechanotransduction perpetuates the myofibroblast phenotype in scleroderma fibrosis. Wound Repair Regen. 2021;29(4):582\u20137.","journal-title":"Wound Repair Regen"},{"issue":"1","key":"2787_CR71","doi-asserted-by":"publisher","first-page":"14010","DOI":"10.1038\/s41598-019-50422-7","volume":"9","author":"LJ Newbury","year":"2019","unstructured":"Newbury LJ, Wang JH, Hung G, Hendry BM, Sharpe CC. Inhibition of Kirsten-Ras reduces fibrosis and protects against renal dysfunction in a mouse model of chronic folic acid nephropathy. Sci Rep. 2019;9(1):14010.","journal-title":"Sci Rep"},{"issue":"5","key":"2787_CR72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127888","volume":"10","author":"H Watanabe-Takano","year":"2015","unstructured":"Watanabe-Takano H, Takano K, Hatano M, Tokuhisa T, Endo T. DA-Raf-mediated suppression of the Ras--ERK pathway is essential for TGF-\u03b21-induced epithelial-mesenchymal transition in alveolar epithelial type 2 cells. PLoS One. 2015;10(5):e0127888.","journal-title":"PLoS One"},{"issue":"17","key":"2787_CR73","doi-asserted-by":"publisher","first-page":"3957","DOI":"10.1038\/sj.emboj.7601818","volume":"26","author":"MK Lee","year":"2007","unstructured":"Lee MK, Pardoux C, Hall MC, Lee PS, Warburton D, Qing J, et al. TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007;26(17):3957\u201367.","journal-title":"EMBO J"},{"key":"2787_CR74","doi-asserted-by":"publisher","first-page":"645044","DOI":"10.3389\/fphys.2021.645044","volume":"12","author":"I Fuentes-Calvo","year":"2021","unstructured":"Fuentes-Calvo I, Martinez-Salgado C. Sos1 modulates extracellular matrix synthesis, proliferation, and migration in fibroblasts. Front Physiol. 2021;12:645044.","journal-title":"Front Physiol"},{"key":"2787_CR75","doi-asserted-by":"crossref","unstructured":"Tzavlaki K, Moustakas A. TGF-\u03b2 Signaling. Biomolecules. 2020;10(3):487.","DOI":"10.3390\/biom10030487"},{"issue":"5","key":"2787_CR76","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1593\/neo.04241","volume":"6","author":"L Xie","year":"2004","unstructured":"Xie L, Law BK, Chytil AM, Brown KA, Aakre ME, Moses HL. Activation of the Erk pathway is required for TGF-\u03b21-induced EMT in vitro. Neoplasia. 2004;6(5):603\u201310.","journal-title":"Neoplasia."},{"issue":"5","key":"2787_CR77","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1002\/jcb.20458","volume":"95","author":"M Davies","year":"2005","unstructured":"Davies M, Robinson M, Smith E, Huntley S, Prime S, Paterson I. Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-\u03b21 involves MAPK, Smad and AP-1 signalling pathways. J Cell Biochem. 2005;95(5):918\u201331.","journal-title":"J Cell Biochem"},{"issue":"4","key":"2787_CR78","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1134\/S0026893321030079","volume":"55","author":"Y-D Kim","year":"2021","unstructured":"Kim Y-D, Choi Y, Na H, Song S-Y, Bae C. MUC4 silencing inhibits TGF-\u03b21-induced epithelial-mesenchymal transition via the ERK1\/2 pathway in human airway epithelial NCI-H292 cells. Mol Biol. 2021;55(4):565\u201372.","journal-title":"Mol Biol"},{"issue":"1","key":"2787_CR79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12931-019-1223-7","volume":"20","author":"C Zhang","year":"2019","unstructured":"Zhang C, Zhu X, Hua Y, Zhao Q, Wang K, Zhen L, et al. YY1 mediates TGF-\u03b21-induced EMT and pro-fibrogenesis in alveolar epithelial cells. Respir Res. 2019;20(1):1\u201311.","journal-title":"Respir Res"},{"key":"2787_CR80","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1755-1536-7-13","volume":"7","author":"P Cipriani","year":"2014","unstructured":"Cipriani P, Di Benedetto P, Capece D, Zazzeroni F, Liakouli V, Ruscitti P, et al. Impaired Cav-1 expression in SSc mesenchymal cells upregulates VEGF signaling: a link between vascular involvement and fibrosis. Fibrogenesis Tissue Repair. 2014;7:13.","journal-title":"Fibrogenesis Tissue Repair"},{"issue":"2","key":"2787_CR81","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/j.0022-202X.2005.23766.x","volume":"125","author":"H Ihn","year":"2005","unstructured":"Ihn H, Yamane K, Tamaki K. Increased phosphorylation and activation of mitogen-activated protein kinase p38 in scleroderma fibroblasts. J Invest Dermatol. 2005;125(2):247\u201355.","journal-title":"J Invest Dermatol"},{"issue":"11","key":"2787_CR82","doi-asserted-by":"publisher","first-page":"7123","DOI":"10.4049\/jimmunol.172.11.7123","volume":"172","author":"Y Asano","year":"2004","unstructured":"Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y, Tamaki K. Phosphatidylinositol 3-kinase is involved in alpha2(I) collagen gene expression in normal and scleroderma fibroblasts. J Immunol. 2004;172(11):7123\u201335.","journal-title":"J Immunol"},{"issue":"1","key":"2787_CR83","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/art.37705","volume":"65","author":"S Serrat\u00ec","year":"2013","unstructured":"Serrat\u00ec S, Chill\u00e0 A, Laurenzana A, Margheri F, Giannoni E, Magnelli L, et al. Systemic sclerosis endothelial cells recruit and activate dermal fibroblasts by induction of a connective tissue growth factor (CCN2)\/transforming growth factor \u03b2-dependent mesenchymal-to-mesenchymal transition. Arthritis Rheum. 2013;65(1):258\u201369.","journal-title":"Arthritis Rheum"},{"issue":"22","key":"2787_CR84","doi-asserted-by":"publisher","first-page":"23098","DOI":"10.1074\/jbc.M311430200","volume":"279","author":"SW Xu","year":"2004","unstructured":"Xu SW, Howat SL, Renzoni EA, Holmes A, Pearson JD, Dashwood MR, et al. Endothelin-1 induces expression of matrix-associated genes in lung fibroblasts through MEK\/ERK. J Biol Chem. 2004;279(22):23098\u2013103.","journal-title":"J Biol Chem"},{"issue":"1","key":"2787_CR85","first-page":"468","volume":"19","author":"J Wen","year":"2019","unstructured":"Wen J, Lin X, Gao W, Qu B, Ling Y, Liu R, et al. MEK inhibition prevents TGF-\u03b21-induced myofibroblast transdifferentiation in human tenon fibroblasts. Mol Med Rep. 2019;19(1):468\u201376.","journal-title":"Mol Med Rep"},{"key":"2787_CR86","doi-asserted-by":"publisher","first-page":"42939","DOI":"10.1038\/srep42939","volume":"7","author":"S Matsuzaki","year":"2017","unstructured":"Matsuzaki S, Pouly JL, Canis M. Effects of U0126 and MK2206 on cell growth and re-growth of endometriotic stromal cells grown on substrates of varying stiffness. Sci Rep. 2017;7:42939.","journal-title":"Sci Rep"},{"issue":"5","key":"2787_CR87","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1111\/j.1464-410X.2009.08465.x","volume":"104","author":"JH Han","year":"2009","unstructured":"Han JH, Lee MY, Myung SC. The effect of endothelin-1 on the production of interleukin-6 in cultured human detrusor smooth muscle cells, and the effect of interleukin-6 on the contractile response of bladder smooth muscle strips from rats. BJU Int. 2009;104(5):707\u201312.","journal-title":"BJU Int"},{"issue":"9","key":"2787_CR88","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1136\/annrheumdis-2018-213031","volume":"77","author":"CP Denton","year":"2018","unstructured":"Denton CP, Ong VH, Xu S, Chen-Harris H, Modrusan Z, Lafyatis R, et al. Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis. Ann Rheum Dis. 2018;77(9):1362\u201371.","journal-title":"Ann Rheum Dis"},{"issue":"14","key":"2787_CR89","doi-asserted-by":"publisher","first-page":"9952","DOI":"10.1074\/jbc.M113.545822","volume":"289","author":"S O'Reilly","year":"2014","unstructured":"O'Reilly S, Ciechomska M, Cant R, van Laar JM. Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-\u03b2 (TGF-\u03b2) signaling promoting SMAD3 activation and fibrosis via Gremlin protein. J Biol Chem. 2014;289(14):9952\u201360.","journal-title":"J Biol Chem"},{"key":"2787_CR90","doi-asserted-by":"crossref","unstructured":"Watanabe T, Baker Frost DA, Mlakar L, Heywood J, da Silveira WA, Hardiman G, et al. A human skin model recapitulates systemic sclerosis dermal fibrosis and identifies COL22A1 as a TGF\u03b2 early response gene that mediates fibroblast to myofibroblast transition. Genes. 2019;10(2):75.","DOI":"10.3390\/genes10020075"},{"issue":"4","key":"2787_CR91","doi-asserted-by":"publisher","first-page":"730","DOI":"10.4161\/cc.11.4.19172","volume":"11","author":"H Kojima","year":"2012","unstructured":"Kojima H, Kunimoto H, Inoue T, Nakajima K. The STAT3-IGFBP5 axis is critical for IL-6\/gp130-induced premature senescence in human fibroblasts. Cell Cycle. 2012;11(4):730\u20139.","journal-title":"Cell Cycle"},{"issue":"5","key":"2787_CR92","doi-asserted-by":"publisher","first-page":"R80","DOI":"10.1186\/bcr2725","volume":"12","author":"K Leslie","year":"2010","unstructured":"Leslie K, Gao SP, Berishaj M, Podsypanina K, Ho H, Ivashkiv L, et al. Differential interleukin-6\/Stat3 signaling as a function of cellular context mediates Ras-induced transformation. Breast Cancer Res. 2010;12(5):R80.","journal-title":"Breast Cancer Res"},{"issue":"6","key":"2787_CR93","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1080\/09168451.2020.1721263","volume":"84","author":"W Ma","year":"2020","unstructured":"Ma W, Huang Q, Xiong G, Deng L, He Y. The protective effect of Hederagenin on pulmonary fibrosis by regulating the Ras\/JNK\/NFAT4 axis in rats. Biosci Biotechnol Biochem. 2020;84(6):1131\u20138.","journal-title":"Biosci Biotechnol Biochem"},{"issue":"6","key":"2787_CR94","doi-asserted-by":"publisher","first-page":"H2946","DOI":"10.1152\/ajpheart.00919.2004","volume":"288","author":"A Zampetaki","year":"2005","unstructured":"Zampetaki A, Zhang Z, Hu Y, Xu Q. Biomechanical stress induces IL-6 expression in smooth muscle cells via Ras\/Rac1-p38 MAPK-NF-kappaB signaling pathways. Am J Physiol Heart Circ Physiol. 2005;288(6):H2946\u201354.","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"12","key":"2787_CR95","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1093\/rheumatology\/keab168","volume":"60","author":"E Adami","year":"2021","unstructured":"Adami E, Viswanathan S, Widjaja AA, Ng B, Chothani S, Zhihao N, et al. IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGF\u03b2-mediated activation of dermal fibroblasts. Rheumatology. 2021;60(12):5820\u20136.","journal-title":"Rheumatology."},{"key":"2787_CR96","doi-asserted-by":"publisher","first-page":"855","DOI":"10.3389\/fphar.2017.00855","volume":"8","author":"X Li","year":"2017","unstructured":"Li X, Zhu L, Wang B, Yuan M, Zhu R. Drugs and targets in fibrosis. Front Pharmacol. 2017;8:855.","journal-title":"Front Pharmacol"},{"issue":"6","key":"2787_CR97","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1358\/dot.2008.44.6.1220138","volume":"44","author":"GA Heresi","year":"2008","unstructured":"Heresi GA, Minai OA. Bosentan in systemic sclerosis. Drugs Today (Barcelona, Spain : 1998). 2008;44(6):415\u201328.","journal-title":"Drugs Today (Barcelona, Spain : 1998)"},{"issue":"3","key":"2787_CR98","first-page":"1739","volume":"19","author":"E Rezus","year":"2020","unstructured":"Rezus E, Burlui AM, Gafton B, Stratulat TA, Zota GR, Cardoneanu A, et al. A patient-centered approach to the burden of symptoms in patients with scleroderma treated with Bosentan: a prospective single-center observational study. Exp Ther Med. 2020;19(3):1739\u201346.","journal-title":"Exp Ther Med"},{"issue":"2","key":"2787_CR99","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1002\/art.24221","volume":"60","author":"L Chung","year":"2009","unstructured":"Chung L, Fiorentino DF, Benbarak MJ, Adler AS, Mariano MM, Paniagua RT, et al. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheumatism. 2009;60(2):584\u201391.","journal-title":"Arthritis Rheumatism"},{"issue":"11","key":"2787_CR100","doi-asserted-by":"publisher","first-page":"3547","DOI":"10.1002\/art.30549","volume":"63","author":"J Pope","year":"2011","unstructured":"Pope J, McBain D, Petrlich L, Watson S, Vanderhoek L, de Leon F, et al. Imatinib in active diffuse cutaneous systemic sclerosis: results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center. Arthritis Rheum. 2011;63(11):3547\u201351.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"2787_CR101","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s13075-019-1981-0","volume":"21","author":"Z Pan","year":"2019","unstructured":"Pan Z, Marra AM, Benjamin N, Eichstaedt CA, Blank N, Bossone E, et al. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study). Arthritis Res Ther. 2019;21(1):217.","journal-title":"Arthritis Res Ther"},{"key":"2787_CR102","doi-asserted-by":"publisher","first-page":"701464","DOI":"10.1155\/2009\/701464","volume":"2009","author":"S Mukherjee","year":"2009","unstructured":"Mukherjee S, Mukherjee U. A comprehensive review of immunosuppression used for liver transplantation. J Transplant. 2009;2009:701464.","journal-title":"J Transplant"},{"key":"2787_CR103","doi-asserted-by":"crossref","unstructured":"Lawrence J, Nho R. The role of the mammalian target of rapamycin (mTOR) in pulmonary fibrosis. Int J Mol Sci. 2018;19(3):778.","DOI":"10.3390\/ijms19030778"},{"key":"2787_CR104","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.yjmcc.2014.09.011","volume":"77","author":"L Xu","year":"2014","unstructured":"Xu L, Yates CC, Lockyer P, Xie L, Bevilacqua A, He J, et al. MMI-0100 inhibits cardiac fibrosis in myocardial infarction by direct actions on cardiomyocytes and fibroblasts via MK2 inhibition. J Mol Cell Cardiol. 2014;77:86\u2013101.","journal-title":"J Mol Cell Cardiol"},{"key":"2787_CR105","first-page":"A7468-A","volume-title":"MMI-0100, a novel MAPKAP kinase II (MK2) inhibitor, delivered via inhalation, displays an excellent safety and tolerability profile in three phase 1 clinical trials. D103 TRANSPLANT AND ILD POTPOURRI","author":"A Luber","year":"2018","unstructured":"Luber A, Peterson C, Panitch A, Wetering J, Hoogdalem E, Nicholson G, et al. MMI-0100, a novel MAPKAP kinase II (MK2) inhibitor, delivered via inhalation, displays an excellent safety and tolerability profile in three phase 1 clinical trials. D103 TRANSPLANT AND ILD POTPOURRI: American Thoracic Society; 2018. p. A7468-A."},{"key":"2787_CR106","doi-asserted-by":"crossref","unstructured":"Meng Q, Bhandary B, Osinska H, James J, Xu N, Shay-Winkler K, et al. MMI-0100 inhibits cardiac fibrosis in a mouse model overexpressing cardiac myosin binding protein C. J Am Heart Assoc. 2017;6(9):e006590.","DOI":"10.1161\/JAHA.117.006590"},{"issue":"Pt A","key":"2787_CR107","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/B978-0-12-416749-0.00012-9","volume":"33","author":"Y Kloog","year":"2013","unstructured":"Kloog Y, Elad-Sfadia G, Haklai R, Mor A. Ras chaperones: new targets for cancer and immunotherapy. Enzymes. 2013;33(Pt A):267\u201389.","journal-title":"Enzymes"},{"issue":"1-2","key":"2787_CR108","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.jneuroim.2010.08.022","volume":"229","author":"E Aizman","year":"2010","unstructured":"Aizman E, Mor A, Chapman J, Assaf Y, Kloog Y. The combined treatment of Copaxone and Salirasib attenuates experimental autoimmune encephalomyelitis (EAE) in mice. J Neuroimmunol. 2010;229(1-2):192\u2013203.","journal-title":"J Neuroimmunol"},{"issue":"16","key":"2787_CR109","doi-asserted-by":"publisher","first-page":"8998","DOI":"10.1111\/jcmm.15533","volume":"24","author":"J Ding","year":"2020","unstructured":"Ding J, Chen YX, Chen Y, Mou Y, Sun XT, Dai DP, et al. Overexpression of FNTB and the activation of Ras induce hypertrophy and promote apoptosis and autophagic cell death in cardiomyocytes. J Cell Mol Med. 2020;24(16):8998\u20139011.","journal-title":"J Cell Mol Med"},{"issue":"5","key":"2787_CR110","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/boc.201400087","volume":"107","author":"E Wolfson","year":"2015","unstructured":"Wolfson E, Schmukler E, Schokoroy ST, Kloog Y, Pinkas-Kramarski R. Enhancing FTS (Salirasib) efficiency via combinatorial treatment. Biol Cell. 2015;107(5):130\u201343.","journal-title":"Biol Cell"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-022-02787-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13075-022-02787-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-022-02787-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T14:10:21Z","timestamp":1668348621000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-022-02787-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,13]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2787"],"URL":"https:\/\/doi.org\/10.1186\/s13075-022-02787-w","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,13]]},"assertion":[{"value":"9 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"108"}}