Dataset Information

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-? type II receptor.

ABSTRACT: Systemic sclerosis (SSc) is a multisystemic fibrotic disease characterized by excessive collagen deposition and extracellular matrix synthesis. Though transforming growth factor-? (TGF-?) plays a fundamental role in the pathogenesis of SSc, the mechanism by which TGF-? signaling acts in SSc remains largely unclear. Here, we showed that TGF-? type II receptor (TGFBR2) was significantly upregulated in both human SSc dermal tissues and primary fibroblasts. In fibroblasts, siRNA-induced knockdown of TGFBR2 resulted in a reduction of p-SMAD2/3 levels and reduced production of type I collagen. Additionally, functional experiments revealed that downregulation of TGFBR2 yielded an anti-growth effect on fibroblasts through inhibiting cell cycle progression. Further studies showed that miR-3606-3p could directly target the 3'-UTR of TGFBR2 and significantly decrease the levels of both TGFBR2 mRNA and protein. Furthermore, SSc dermal tissues and primary fibroblasts contain significantly reduced amounts of miR-3606-3p, and the overexpression of miR-3606-3p in fibroblasts replicates the phenotype of TGFBR2 downregulation. Collectively, our findings demonstrated that increased TGFBR2 could be responsible for the hyperactive TGF-? signaling observed in SSc. Moreover, we identified a pivotal role for miR-3606-3p in SSc, which acts, at least partly, through the attenuation of TGF-? signaling via TGFBR2 repression, suggesting that the regulation of miR-3606-3p/TGFBR2 could be a promising therapeutic target that could improve the treatment strategy for fibrosis.

SUBMITTER: Shi X

PROVIDER: S-EPMC6224271 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor.

Shi Xiangguang X Liu Qingmei Q Li Na N Tu Wenzhen W Luo Ruoyu R Mei Xueqian X Ma Yanyun Y Xu Weihong W Chu Haiyan H Jiang Shuai S Du Zhimin Z Zhao Han H Zhao Liang L Jin Li L Wu Wenyu W Wang Jiucun J

Cell cycle (Georgetown, Tex.) 20180917 16

Systemic sclerosis (SSc) is a multisystemic fibrotic disease characterized by excessive collagen deposition and extracellular matrix synthesis. Though transforming growth factor-β (TGF-β) plays a fundamental role in the pathogenesis of SSc, the mechanism by which TGF-β signaling acts in SSc remains largely unclear. Here, we showed that TGF-β type II receptor (TGFBR2) was significantly upregulated in both human SSc dermal tissues and primary fibroblasts. In fibroblasts, siRNA-induced knockdown of ...[more]

PMID: 30145936

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Dataset Information

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-? type II receptor.

Publications

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor.

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