博莱霉素
SMAD公司
纤维化
流式细胞术
细胞凋亡
体内
癌症研究
转化生长因子
化学
生物
病理
医学
免疫学
内分泌学
内科学
生物化学
生物技术
化疗
作者
Xiaoqing Xie,Haina Gan,Jing Tian,Fen Li,Jinwei Chen,Jia Wang,Jia‐Feng Liao,Shu Li
摘要
Iguratimod (T-614), exerting a powerful anti-inflammatory ability, has therapeutic efficacy in multiple autoimmune diseases. However, the effect of T-614 on systemic sclerosis (SSc) is unclear. Here, we investigate the effect and molecular mechanism of T-614 in experimental SSc models.In vitro, cultured dermal fibroblasts from four SSc patients were subjected to different doses of T-614 in the presence or absence of TGF-β1 stimulation. Cell proliferation, apoptosis and migration were determined by CCK-8, flow cytometry and transwell assay, respectively. Fibrosis markers and smad signalling pathway-related proteins were detected by immunoblotting and immunofluorescence. In vivo, a bleomycin-induced SSc mouse model was used to evaluate the effect of T-614 on skin fibrosis. Pathological changes in skin tissues were evaluated by HE, Masson staining and immunohistochemistry.In the study, we found T-614 inhibited TGF-β1-induced cell proliferation, migration and promoted apoptosis in a dose-dependent manner (all p < 0.01). T-614 partially reversed TGF-β1-induced upregulation of fibrosis markers and phosphorylation of smad2 and smad3 and blocked p-Smad3 nuclear translocation (all p < 0.05), suggesting T-614 may inhibit dermal fibroblasts activation by regulating TGF-β1/smad pathway. In vivo experiments, T-614 alleviated skin thickness in bleomycin-induced SSc mice (all p < 0.05). The expression of fibrosis markers and the infiltration of macrophages in skin tissue were significantly decreased after T-614 treatment (all p < 0.05).Our preliminary data indicated T-614 inhibited dermal fibroblasts activation and skin fibrosis at least partly by regulating TGF-β1/smad pathway in experimental SSc models and may be a promising therapeutic agent for SSc.
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