title: A conserved TGFβ1/HuR feedback circuit regulates the fibrogenic response in fibroblasts.
abstract: Persistent fibroblast activation in wound repair is believed to be the key reason for fibrosis and transforming growth factor (TGF)β is considered as one of the key mediators for the fibrogenic response, with the detailed mechanism largely unknown. Here we found that TGFβ1 treatment could induce a significant increase of endogenous TGFβ1 expression by enhancing the mRNA stability in cardiac fibroblasts. Further study revealed that TGFβ1 treatment translocated the nuclear HuR into cytoplasm, which in turn bound the ARE in the 3'UTR of TGFβ1 and increased the mRNA stability as seen from the RNA-IP and reporter assay. Knockdown of HuR decreased the endogenous expression of TGFβ1 under exogenous TGFβ1 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression. Our study here established a TGFβ1/HuR feedback circuit regulating the fibrogenic response in fibroblasts, and targeting this feedback loop is of great potential to control fibrosis.
authors.affiliation: Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Danna
authors.initials: D
authors.lastname: Bai
authors.forename: Qun
authors.initials: Q
authors.lastname: Gao
authors.forename: Chengxiang
authors.initials: C
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Ge
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D051959:ELAV Proteins / Q000378:metabolism*; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005355:Fibrosis / Q000188:drug therapy; D005786:Gene Expression Regulation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000166:cytology; D011401:Promoter Regions, Genetic; D020871:RNA Stability / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases