title: Role of endothelin-1 in the skin fibrosis of systemic sclerosis.
abstract: Endothelin-1 (ET-1) acts as a key regulator of vasoconstriction and fibrosis. Many previous studies have focused on the role of ET-1 in scleroderma (systemic sclerosis, SSc). We investigated the effects of ET-1 on the production of extracellular matrix in SSc and normal skin fibroblasts. Primary cultured dermal fibroblasts from SSc patients and healthy controls were treated with ET-1 (25 ng/mL) for 0 min, 15 min, 1 h, 24 h, 48 h and 72 h, respectively. Our results showed that, in SSc fibroblasts, ET-1 upregulated collagen type I, connective tissue growth factor (CTGF), type I plasminogen activator inhibitor (PAI-1) and pAkt in a time-dependent manner within 72 h; in normal fibroblasts, 25 ng/mL ET-1 stimulation correlated with high levels of CTGF, PAI-1 and pAkt. The secretion of fibronectin (FN), collagen type I, and PAI-1 is markedly increased in the supernatant of both SSc fibroblasts and normal fibroblasts. Furthermore, ET-1 phosphorylates Smad2 and Smad3 in normal fibroblasts, but not in SSc fibroblasts. In conclusion, our results demonstrated that ET-1 may induce fibrosis in dermal fibroblasts through Akt signals.
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Jing
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: T T
authors.initials: TT
authors.lastname: Dou
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: X B
authors.initials: XB
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: H L
authors.initials: HL
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Min
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Cai
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Man
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000096:biosynthesis / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; D024042:Collagen Type I; D019332:Endothelin-1; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C051321:SERPINE1 protein, human; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D055513:Connective Tissue Growth Factor; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; endothelin-1; fibroblast; smad; systemic sclerosis