Effects of p-CREB-1 on transforming growth factor-β3 auto-regulation in hepatic stellate cells

✍ Scribed by Liang Deng; Ying Li; Jin ming Huang; Guan yu Zhou; Wei Qian; Ke shu Xu

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 630 KB
• Volume: 112
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.23017

✦ Synopsis

Abstract

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.