A conserved TGF尾1/HuR feedback circuit regulates the fibrogenic response in fibroblasts

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• 作者：Danna Bai^a ; ^b ; ¹ ; Qun Gao^a ; ^b ; ¹ ; Chengxiang Li^a ; ¹ ; Lan Ge^c ; Yan Gao^b ; Haichang Wang^a ; ^{haichangwang00@yahoo.cn}
• 关键词：TGF尾 ; transforming growth factor 尾 ; HuR ; human antigen R ; AREs ; AU-rich elements ; UTR ; untranslated region ; RNA-IP ; RNA immunoprecipitation ; p38MAPK ; p38 mitogen-activated protein kinase ; HSP27 ; heat shock protein 27 ; Col1a ; collagen type I alpha ; Col3a
• 刊名：Cellular Signalling
• 出版年：2012
• 期刊代码：42_08986568
• 类别：bio
• 出版时间：July, 2012
• 卷：24
• 期：7
• 页码：1426-1432
• 文件大小：875 K

摘要

Persistent fibroblast activation in wound repair is believed to be the key reason for fibrosis and transforming growth factor (TGF)尾 is considered as one of the key mediators for the fibrogenic response, with the detailed mechanism largely unknown. Here we found that TGF尾1 treatment could induce a significant increase of endogenous TGF尾1 expression by enhancing the mRNA stability in cardiac fibroblasts. Further study revealed that TGF尾1 treatment translocated the nuclear HuR into cytoplasm, which in turn bound the ARE in the 3鈥睻TR of TGF尾1 and increased the mRNA stability as seen from the RNA-IP and reporter assay. Knockdown of HuR decreased the endogenous expression of TGF尾1 under exogenous TGF尾1 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression. Our study here established a TGF尾1/HuR feedback circuit regulating the fibrogenic response in fibroblasts, and targeting this feedback loop is of great potential to control fibrosis.