title: MicroRNA-21 in scleroderma fibrosis and its function in TGF-β-regulated fibrosis-related genes expression.
abstract: Uncontrolled fibrosis in multiple organs is the main cause of death in systemic sclerosis (SSc), and transforming growth factor-β (TGF-β) activation plays a fundamental role in the process. Our previous study demonstrated that miR-21 was significantly up-regulated in SSc fibroblasts. Here, we found that TGF-β regulated the expression of miR-21 and fibrosis-related genes, and decreased Smad7 expression. Over-expression of miR-21 in fibroblasts decreased the levels of Smad7, whereas knockdown of miR-21 increased its expression. Further study using a reporter gene assay demonstrated Smad7 was a direct target of miR-21. Similar to human SSc, the expression of miR-21 increased in the bleomycin induced skin fibrosis. Inhibition of fibrosis by treatment with anti-fibrosis drug bortezomib restored the levels of miR-21 and Smad7. MiR-21 may function in an amplifying circuit to enhance TGF-β signaling events in SSc fibrosis, and suggesting that miR-21 may act as a potential therapeutic target.
authors: Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Honglin
authors: H
authors: Zhu
authors: Hui
authors: H
authors: Luo
authors: Yisha
authors: Y
authors: Li
authors: Yaou
authors: Y
authors: Zhou
authors: Ying
authors: Y
authors: Jiang
authors: Jin
authors: J
authors: Chai
authors: Xianzhong
authors: X
authors: Xiao
authors: Yunhui
authors: Y
authors: You
authors: Xiaoxia
authors: X
authors: Zuo
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000378:metabolism; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D035683:MicroRNAs / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D011719:Pyrazines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D045743:Scleroderma, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction; D012867:Skin / Q000473:pathology; D051906:Smad7 Protein / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D001897:Boronic Acids; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011719:Pyrazines; D034741:RNA, Small Interfering; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D000069286:Bortezomib
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