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| Serpine1SummaryGene Symbol: Serpine1 Description: serine (or cysteine) peptidase inhibitor, clade E, member 1 Alias: PAI-1, PAI1, Planh1, plasminogen activator inhibitor 1, PAI, Plasminogen activator inhibitor-1 precursor (PAI-1) (Endothelial plasminogen activator inhibitor) (PAI), endothelial plasminogen activator inhibitor, nexin, plasminogen activator inhibitor type 1, plasminogen activator inhibitor, type I, serine (or cysteine) proteinase inhibitor, clade E, member 1, serpin E1 Species: mouse Products: Serpine1 Top Publications
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- Kitching A, Kong Y, Huang X, Davenport P, Edgtton K, Carmeliet P, et al. Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 2003;14:1487-95 pubmed..Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis by inhibiting plasminogen activators and has effects on leukocyte recruitment and matrix ..
- He W, Tan R, Dai C, Li Y, Wang D, Hao S, et al. Plasminogen activator inhibitor-1 is a transcriptional target of the canonical pathway of Wnt/beta-catenin signaling. J Biol Chem. 2010;285:24665-75 pubmed publisherPlasminogen activator inhibitor-1 (PAI-1) is a multifunctional glycoprotein that plays a critical role in the pathogenesis of chronic kidney and cardiovascular diseases...
- Carmeliet P, Kieckens L, Schoonjans L, Ream B, van Nuffelen A, Prendergast G, et al. Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by homologous recombination and characterization. J Clin Invest. 1993;92:2746-55 pubmedHomozygous plasminogen activator inhibitor-1 (PAI-1)-deficient (PAI-1-/-) mice were generated by homologous recombination in D3 embryonic stem cells...
- Maillard C, Bouquet C, Petitjean M, Mestdagt M, Frau E, Jost M, et al. Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with transgenic ocular tumors. Carcinogenesis. 2008;29:2236-42 pubmed publisher..We studied the impact of plasminogen activator inhibitor (PAI)-1 deficiency in a transgenic mouse model of ocular tumors originating from retinal epithelial cells and leading to ..
- Chuang Tsai S, Sisson T, Hattori N, Tsai C, Subbotina N, Hanson K, et al. Reduction in fibrotic tissue formation in mice genetically deficient in plasminogen activator inhibitor-1. Am J Pathol. 2003;163:445-52 pubmedMice with homozygous deletion of the plasminogen activator inhibitor-1 gene (PAI-1(-/-)) are relatively protected from bleomycin-induced pulmonary fibrosis...
- Hattori N, Degen J, Sisson T, Liu H, Moore B, Pandrangi R, et al. Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice. J Clin Invest. 2000;106:1341-50 pubmedMice deleted for the plasminogen activator inhibitor-1 (PAI-1) gene are relatively protected from developing pulmonary fibrosis induced by bleomycin...
- Eitzman D, McCoy R, Zheng X, Fay W, Shen T, Ginsburg D, et al. Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene. J Clin Invest. 1996;97:232-7 pubmed..transgenic mice that either overexpressed or were completely deficient in murine plasminogen activator inhibitor-1 (PAI-1). 2 wk after 0...
- Ghosh A, Bradham W, Gleaves L, De Taeye B, Murphy S, Covington J, et al. Genetic deficiency of plasminogen activator inhibitor-1 promotes cardiac fibrosis in aged mice: involvement of constitutive transforming growth factor-beta signaling and endothelial-to-mesenchymal transition. Circulation. 2010;122:1200-9 pubmed publisherElevated levels of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of urokinase plasminogen activator and tissue plasminogen activator, are implicated in the pathogenesis of tissue fibrosis...
- Eitzman D, Westrick R, Xu Z, Tyson J, Ginsburg D. Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood. 2000;96:4212-5 pubmedDissolution of the fibrin blood clot is regulated in large part by plasminogen activator inhibitor-1 (PAI-1)...
- Tamura Y, Kawao N, Okada K, Yano M, Okumoto K, Matsuo O, et al. Plasminogen activator inhibitor-1 is involved in streptozotocin-induced bone loss in female mice. Diabetes. 2013;62:3170-9 pubmed publisher..In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1-deficient mice...
- Sjöland H, Eitzman D, Gordon D, Westrick R, Nabel E, Ginsburg D. Atherosclerosis progression in LDL receptor-deficient and apolipoprotein E-deficient mice is independent of genetic alterations in plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol. 2000;20:846-52 pubmed..Plasminogen activator inhibitor type 1 (PAI-1) is the primary inhibitor of plasminogen activation and has been proposed to promote atherosclerosis by ..
- Samarakoon R, Higgins S, Higgins C, Higgins P. TGF-beta1-induced plasminogen activator inhibitor-1 expression in vascular smooth muscle cells requires pp60(c-src)/EGFR(Y845) and Rho/ROCK signaling. J Mol Cell Cardiol. 2008;44:527-38 pubmed publisherTGF-beta1 and its target gene encoding plasminogen activator inhibitor-1 (PAI-1) are major causative factors in the pathology of tissue fibrosis and vascular disease...
- Yamamoto K, Shimokawa T, Yi H, Isobe K, Kojima T, Loskutoff D, et al. Aging accelerates endotoxin-induced thrombosis : increased responses of plasminogen activator inhibitor-1 and lipopolysaccharide signaling with aging. Am J Pathol. 2002;161:1805-14 pubmed..Since elevated plasminogen activator inhibitor-1 (PAI-1) primarily contributes to endotoxin-induced thrombosis, we first compared the induction of PAI-1 by ..
- Park Y, Liu G, Lorne E, Zhao X, Wang J, Tsuruta Y, et al. PAI-1 inhibits neutrophil efferocytosis. Proc Natl Acad Sci U S A. 2008;105:11784-9 pubmed publisher..Plasma and tissue levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, are elevated in inflammatory conditions, including sepsis and acute lung injury, ..
- Gutierrez L, Schulman A, Brito Robinson T, Noria F, Ploplis V, Castellino F. Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res. 2000;60:5839-47 pubmed..deficiencies in urokinase-type plasminogen activator (UPA-/-) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1-/-), was studied using a fibrosarcoma tumor model. Murine T241 fibrosarcoma cells were s.c...
- Schafer K, Müller K, Hecke A, Mounier E, Goebel J, Loskutoff D, et al. Enhanced thrombosis in atherosclerosis-prone mice is associated with increased arterial expression of plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol. 2003;23:2097-103 pubmed..was undertaken to investigate the origin and pathophysiological importance of plasminogen activator inhibitor (PAI-1) in atherosclerosis...
- Ploplis V, Balsara R, Sandoval Cooper M, Yin Z, Batten J, Modi N, et al. Enhanced in vitro proliferation of aortic endothelial cells from plasminogen activator inhibitor-1-deficient mice. J Biol Chem. 2004;279:6143-51 pubmedA number of studies have identified a role for plasminogen activator inhibitor-1 (PAI-1) in regulating angiogenesis, although results from these investigations have been controversial...
- Xu Z, Castellino F, Ploplis V. Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture. Blood. 2010;115:2038-47 pubmed publisherAlthough the involvement of plasminogen activator inhibitor-1 (PAI-1) in fibrotic diseases is well documented, its role in cardiac fibrosis remains controversial...
- Pinsky D, Liao H, Lawson C, Yan S, Chen J, Carmeliet P, et al. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest. 1998;102:919-28 pubmed..Plasma levels of plasminogen activator inhibitor-1 (PAI-1) antigen, detected by ELISA, increased in a time-dependent fashion after hypoxic exposure (increased as early as ..
- Wang H, Zhang Y, Heuckeroth R. PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through activation of tPA. FEBS Lett. 2007;581:3098-104 pubmedPlasminogen activator inhibitor-1 (PAI-1) increases injury in several liver, lung and kidney disease models...
- Smith L, Dixon J, Stringham J, Eren M, Elokdah H, Crandall D, et al. Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis. Blood. 2006;107:132-4 pubmed..While the pathogenesis of VOD is uncertain, plasminogen activator inhibitor-1 (PAI-1) has emerged as a diagnostic marker and predictor of VOD in humans...
- Almholt K, Nielsen B, Frandsen T, Brunner N, Danø K, Johnsen M. Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice. Oncogene. 2003;22:4389-97 pubmedThe plasminogen activator inhibitor-1 (PAI-1) blocks the activation of plasmin(ogen), an extracellular protease vital to cancer invasion...
- Moriwaki H, Stempien Otero A, Kremen M, Cozen A, Dichek D. Overexpression of urokinase by macrophages or deficiency of plasminogen activator inhibitor type 1 causes cardiac fibrosis in mice. Circ Res. 2004;95:637-44 pubmed..we hypothesized that elevated activity of uPA or deficiency of the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) might cause cardiac fibrosis...
- Jost M, Maillard C, Lecomte J, Lambert V, Tjwa M, Blaise P, et al. Tumoral and choroidal vascularization: differential cellular mechanisms involving plasminogen activator inhibitor type I. Am J Pathol. 2007;171:1369-80 pubmedAn adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis...
- Kenny S, Gamble J, Lyons S, Vlatkovic N, Dimaline R, Varro A, et al. Gastric expression of plasminogen activator inhibitor (PAI)-1 is associated with hyperphagia and obesity in mice. Endocrinology. 2013;154:718-26 pubmed publisherThe adipokine plasminogen activator inhibitor (PAI)-1 is increased in plasma of obese individuals and exhibits increased expression in the stomachs of individuals infected with Helicobacter...
- Pedroja B, Kang L, Imas A, Carmeliet P, Bernstein A. Plasminogen activator inhibitor-1 regulates integrin alphavbeta3 expression and autocrine transforming growth factor beta signaling. J Biol Chem. 2009;284:20708-17 pubmed publisher..transforming growth factor beta (TGFbeta) signaling, resulting in extracellular matrix accumulation and increased PAI-1 (plasminogen activator inhibitor) expression...
- Carmeliet P, Stassen J, Schoonjans L, Ream B, van den Oord J, De Mol M, et al. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis. J Clin Invest. 1993;92:2756-60 pubmedThe effects of plasminogen activator inhibitor-1 (PAI-1) gene inactivation on hemostasis, thrombosis and thrombolysis were studied in homozygous PAI-1-deficient (PAI-1-/-) mice, generated by homologous recombination in D3 embryonic stem ..
- Oishi K, Uchida D, Ohkura N, Horie S. PPAR? deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR? activation in the liver. Biochem Biophys Res Commun. 2010;401:313-8 pubmed publisherAn increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals...
- Oh C, Ariue B, Alban R, Shaw B, Cho S. PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model. Biochem Biophys Res Commun. 2002;294:1155-60 pubmed..We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis...
- Bajou K, Maillard C, Jost M, Lijnen R, Gils A, Declerck P, et al. Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth. Oncogene. 2004;23:6986-90 pubmedPlasminogen activator inhibitor type 1 (PAI-1) plays a key role in tumor progression and is believed to control proteolytic activity and cell migration during angiogenesis...
- Labied S, Blacher S, Carmeliet P, Noel A, Frankenne F, Foidart J, et al. Transient reduction of placental angiogenesis in PAI-1-deficient mice. Physiol Genomics. 2011;43:188-98 pubmed publisher..Plasminogen activator inhibitor-1 (PAI-1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at 10.5-11.5 days postcoitum (dpc)...
- Ma L, Mao S, Taylor K, Kanjanabuch T, Guan Y, Zhang Y, et al. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes. 2004;53:336-46 pubmedIncreased plasminogen activator inhibitor 1 (PAI-1) has been linked to not only thrombosis and fibrosis but also to obesity and insulin resistance. Increased PAI-1 levels have been presumed to be consequent to obesity...
- Kwak S, Wang X, He Q, Fang W, Mitra S, Bdeir K, et al. Plasminogen activator inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK-mediated pathway. Thromb Haemost. 2006;95:829-35 pubmedPlasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor superfamily, modulates fibrinolysis by interacting with proteolytic mediators, including urokinase plasminogen activator (uPA)...
- Bajou K, Peng H, Laug W, Maillard C, Noel A, Foidart J, et al. Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell. 2008;14:324-34 pubmed publisherPlasminogen activator inhibitor-1 (PAI-1) paradoxically enhances tumor progression and angiogenesis; however, the mechanism supporting this role is not known...
- Otsuka G, Agah R, Frutkin A, Wight T, Dichek D. Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways. Arterioscler Thromb Vasc Biol. 2006;26:737-43 pubmed..downstream mediator of TGF-beta1-induced intimal growth, we transduced carotid arteries of PAI-1-deficient (Serpine1(-/-)) mice with the TGF-beta1-expressing vector...
- Oh S, Seki T, Goss K, Imamura T, Yi Y, Donahoe P, et al. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A. 2000;97:2626-31 pubmed..Taken together, our results suggest that the balance between the ALK1 and ALK5 signaling pathways in endothelial cells plays a crucial role in determining vascular endothelial properties during angiogenesis. ..
- Jiang Q, Gingles N, Olivier M, Miles L, Parmer R. The anti-fibrinolytic SERPIN, plasminogen activator inhibitor 1 (PAI-1), is targeted to and released from catecholamine storage vesicles. Blood. 2011;117:7155-63 pubmed publisherRecent studies suggest a crucial role for plasminogen activator inhibitor-1 (PAI-1) in mediating stress-induced hypercoagulability and thrombosis. However, the mechanisms by which PAI-1 is released by stress are not well-delineated...
- Ploplis V, Cornelissen I, Sandoval Cooper M, Weeks L, Noria F, Castellino F. Remodeling of the vessel wall after copper-induced injury is highly attenuated in mice with a total deficiency of plasminogen activator inhibitor-1. Am J Pathol. 2001;158:107-17 pubmed..system on both early and late stages of this disease, mice deficient for plasminogen activator inhibitor-1 (PAI-1(-/-)) were used in a model of vascular injury/repair, and the resulting phenotype compared to that of wild-type (..
- DiMusto P, Lu G, Ghosh A, Roelofs K, Su G, Zhao Y, et al. Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model. Am J Physiol Heart Circ Physiol. 2012;302:H1378-86 pubmed publisherThe serine proteases, along with their inhibitor plasmin activator inhibitor-1 (PAI-1), have been shown to play a role in abdominal aortic aneurysm (AAA) formation...
- McMahon G, Petitclerc E, Stefansson S, Smith E, Wong M, Westrick R, et al. Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis. J Biol Chem. 2001;276:33964-8 pubmedElevated expression of plasminogen activator inhibitor-1 (PAI-1) in tumors is associated with a poor prognosis in many cancers. Reduced tumor growth and angiogenesis have also been reported in mice deficient in PAI-1...
- Lijnen H, Maquoi E, Morange P, Voros G, Van Hoef B, Kopp F, et al. Nutritionally induced obesity is attenuated in transgenic mice overexpressing plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol. 2003;23:78-84 pubmedThe objective of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue development in vivo...
- Abderrahmani R, François A, Buard V, Tarlet G, Blirando K, Hneino M, et al. PAI-1-dependent endothelial cell death determines severity of radiation-induced intestinal injury. PLoS ONE. 2012;7:e35740 pubmed publisher..Recently, plasminogen activator inhibitor type 1 (SERPINE1/PAI-1) was reported as an essential mediator of late radiation-induced intestinal injury...
- De Taeye B, Novitskaya T, Gleaves L, Covington J, Vaughan D. Bone marrow plasminogen activator inhibitor-1 influences the development of obesity. J Biol Chem. 2006;281:32796-805 pubmedPlasma levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in obesity and correlate with body mass index...
- Liu R, Choi J, Wu J, Gaston Pravia K, Lewis K, Brand J, et al. Oxidative modification of nuclear mitogen-activated protein kinase phosphatase 1 is involved in transforming growth factor beta1-induced expression of plasminogen activator inhibitor 1 in fibroblasts. J Biol Chem. 2010;285:16239-47 pubmed publisher..RNA enhances TGF-beta1-induced phosphorylation of JNK and p38 as well as the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-beta-responsive gene involved in the pathogenesis of many diseases...
- Milliat F, Sabourin J, Tarlet G, Holler V, Deutsch E, Buard V, et al. Essential role of plasminogen activator inhibitor type-1 in radiation enteropathy. Am J Pathol. 2008;172:691-701 pubmed publisher..involved in radiation-induced damage, we hypothesized that its target gene, plasminogen activator inhibitor type 1 (PAI-1), is an essential mediator of intestinal radiation toxicity...
- Keller T, van der Sluijs K, de Kruif M, Gerdes V, Meijers J, Florquin S, et al. Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1. Circ Res. 2006;99:1261-9 pubmed..Thrombin generation was not changed in hyperfibrinolytic mice, deficient in plasminogen activator inhibitor type-1 (PAI-1(-/-)); however, increased fibrin degradation was seen...
- Nordstrom S, Carleton S, Carson W, Eren M, Phillips C, Vaughan D. Transgenic over-expression of plasminogen activator inhibitor-1 results in age-dependent and gender-specific increases in bone strength and mineralization. Bone. 2007;41:995-1004 pubmedThe plasminogen activation system (PAS) and its principal inhibitor, plasminogen activator inhibitor-1 (PAI-1), are recognized modulators of matrix...
- Devy L, Blacher S, Grignet Debrus C, Bajou K, Masson V, Gerard R, et al. The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J. 2002;16:147-54 pubmedb>Plasminogen activator inhibitor 1 (PAI-1) is believed to control proteolytic activity and cell migration during angiogenesis...
- Brown N, Bradford J, Wang Z, Lea W, Ma L, Ma J, et al. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney Int. 2007;72:72-81 pubmedAngiotensin (Ang) II stimulates plasminogen activator inhibitor-1 (PAI-1) expression in many cell types by mechanisms that are cell-type specific...
- Ploplis V. Effects of altered plasminogen activator inhibitor-1 expression on cardiovascular disease. Curr Drug Targets. 2011;12:1782-9 pubmedPlasminogen Activator Inhibitor-1 (PAI-1) is a multifunctional protein with the ability to not only regulate fibrinolysis through inhibition of plasminogen activation, but also cell signaling events which have direct downstream effects ..
- Li M, Li C, Liu Y, Xing Y, Hu L, Borok Z, et al. Mesodermal deletion of transforming growth factor-beta receptor II disrupts lung epithelial morphogenesis: cross-talk between TGF-beta and Sonic hedgehog pathways. J Biol Chem. 2008;283:36257-64 pubmed publisher..To our knowledge, this is the first in vivo evidence for a reciprocal and novel mode of cross-communication between Shh and TGF-beta pathways during embryonic development. ..
- Tateossian H, Morse S, Simon M, Dean C, Brown S. Interactions between the otitis media gene, Fbxo11, and p53 in the mouse embryonic lung. Dis Model Mech. 2015;8:1531-42 pubmed publisher..Overall, our results support the conclusion that FBXO11 regulates the TGF-β pathway in the embryonic lung via cross-talk with p53. ..
- Basu A, Menicucci G, Maestas J, Das A, McGuire P. Plasminogen activator inhibitor-1 (PAI-1) facilitates retinal angiogenesis in a model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2009;50:4974-81 pubmed publisher..present study was to investigate the role of the serine proteinase inhibitor plasminogen activator inhibitor -1 (PAI-1) in facilitating retinal angiogenesis...
- Halappanavar S, Stampfli M, Berndt Weis L, Williams A, Douglas G, Yauk C. Toxicogenomic analysis of mainstream tobacco smoke-exposed mice reveals repression of plasminogen activator inhibitor-1 gene in heart. Inhal Toxicol. 2009;21:78-85 pubmed..genes, cytochrome P-450 1A1 (Cyp1A1) was upregulated by 12-fold, and Serpine-1 (plasminogen activator inhibitor-1, PAI-1) was downregulated by 1.7-fold...
- Oishi K, Ohkura N, Ishida N. Adrenal gland-dependent augmentation of plasminogen activator inhibitor-1 expression in streptozotocin-induced diabetic mice. J Thromb Haemost. 2006;4:1566-74 pubmed..of cardiac events, and one risk factor for infarction is an elevated level of plasminogen activator inhibitor-1 (PAI-1)...
- Hamasaki Y, Doi K, Maeda Mamiya R, Ogasawara E, Katagiri D, Tanaka T, et al. A 5-hydroxytryptamine receptor antagonist, sarpogrelate, reduces renal tubulointerstitial fibrosis by suppressing PAI-1. Am J Physiol Renal Physiol. 2013;305:F1796-803 pubmed publisher..Additionally, results showed that mRNA expression of plasminogen activator inhibitor-1 (PAI-1), which is known to promote fibrosis by mediating and enhancing transforming growth factor (TGF)-?1 signaling, ..