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Effects of p‐CREB‐1 on transforming growth factor‐β3 auto‐regulation in hepatic stellate cells
Author(s) -
Deng Liang,
Li Ying,
Huang Jin ming,
Zhou Guan yu,
Qian Wei,
Xu Ke shu
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23017
Subject(s) - hepatic stellate cell , transforming growth factor , creb , microbiology and biotechnology , growth factor , chemistry , cancer research , medicine , endocrinology , biology , transcription factor , receptor , biochemistry , gene
Previous studies have demonstrated that transforming growth factor‐β3 (TGF‐β3) protected liver against fibrosis in vivo and vitro, but its regulation is poorly understood. In addition, the cAMP‐responsive element (CRE) in TGF‐β3 promoter is recognized as an important regulatory site for TGF‐β3 auto‐regulation. Thus, we hypothesize that transcription factor CRE‐binding protein‐1 (CREB‐1) regulates the auto‐induction of TGF‐β3 in hepatic stellate cells (HSCs). We used exogenous TGF‐β3 to activate the signal pathway of TGF‐β3 auto‐regulation in HSCs, results indicated that exogenous TGF‐β3 could up‐regulate the protein and mRNA expressions of TGF‐β3, and provoke the phosphorylation of CREB‐1 on Ser‐133, besides, it could induce the DNA binding activity of p‐CREB‐1 and activate TGF‐β3 promoter as well. Additionally, we used pGenesil‐1.1‐shRNA‐CREB‐1 and pRSV‐CREB‐1 expression vector to silence and up‐regulate CREB‐1 gene expression respectively, and the results indicated that inhibition of CREB‐1 suppressed exogenous TGF‐β3 stimulation of TGF‐β3 mRNA and protein expressions in HSCs, whereas up‐regulation of CREB‐1 induced this stimulation. Our results indicate that exogenous TGF‐β3 up‐regulates the activity of TGF‐β3 promoter by activating CREB‐1, then induces the mRNA and protein expressions of TGF‐β3. Especially, p‐CREB‐1 is a critical transcription factor in mediating TGF‐β3 auto‐induction. J. Cell. Biochem. 112: 1046–1054, 2011. © 2011 Wiley‐Liss, Inc.