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 throughAkt signals.

Mir‐217 promotes inflammation and fibrosis in high glucose cultured rat glomerular mesangial cells via Sirt1/HIF‐1α signaling pathway

“…The interaction between chronic inflammation and renal interstitial fibrosis promotes the occurrence and development of DN . Endothelin‐1 promotes the expression of fibrosis factors, such as vascular endothelial growth factor (VEGF) , fibronectin and connective tissue growth factor (CTGF) as an inflammatory stimulus , and thus aggravates inflammation and fibrosis. In recent years, researches confirmed that, Sirtuin (Sirt) protein family plays an important role in age‐related diseases and metabolic diseases.…”

Raynaud’s Phenomenon

“…Increased expression of endothelin-1 in the skin of SSc patients was also detected [25]. Besides its properties of vasoconstrictor, it has been confirmed that endothelin-1 promotes fibrosis in scleroderma patients [26]. In SSc, endothelial injury represents a key pathogenic step that mediates the processes of inflammation, thrombus formation, and fibrosis [23].…”

Role of hypoxia‐inducible factor 1α as a potential biomarker for renal diseases—A systematic review

“…[53][54][55][56] DN is one of the main complications of diabetes mellitus, characterized by glomerular basement membrane thickening, glomerular hypertrophy, and accumulation of proteins in the extracellular matrix, leading to glomerular and interstitial fibrosis. 24,57,58 The main factors that corroborate the development of this disease are hyperglycemia, accumulations of advanced glycosylation end products (AGE), oxidative stress, cytokines, transforming growth factor β (TGF-β), 59-61 vascular endothelial growth factor (VEGF) expression, increased fibronectin expression, and connective tissue growth factor (CTGF) 58,62 ; these factors stimulate the inflammatory process and, consequently, aggravate inflammation and fibrosis. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.…”

“…The main factors that corroborate the development of this disease are hyperglycemia, accumulations of advanced glycosylation end products (AGE), oxidative stress, cytokines, transforming growth factor β (TGF‐β), vascular endothelial growth factor (VEGF) expression, increased fibronectin expression, and connective tissue growth factor (CTGF); these factors stimulate the inflammatory process and, consequently, aggravate inflammation and fibrosis.…”