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01-08-2013 | Original Research

MicroRNA-21 in Scleroderma Fibrosis and its Function in TGF-β- Regulated Fibrosis-Related Genes Expression

Authors: Honglin Zhu, Hui Luo, Yisha Li, Yaou Zhou, Ying Jiang, Jin Chai, Xianzhong Xiao, Yunhui You, Xiaoxia Zuo

Published in: Journal of Clinical Immunology | Issue 6/2013

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.

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Title: MicroRNA-21 in Scleroderma Fibrosis and its Function in TGF-β- Regulated Fibrosis-Related Genes Expression
Authors: Honglin Zhu
Hui Luo
Yisha Li
Yaou Zhou
Ying Jiang
Jin Chai
Xianzhong Xiao
Yunhui You
Xiaoxia Zuo
Publication date: 01-08-2013
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 6/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-013-9896-z

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