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Effects of p-CREB-1 on transforming growth factor-beta3 auto-regulation in hepatic stellate cells.

Authors: Deng, L  Li, Y  Huang, JM  Zhou, GY  Qian, W  Xu, KS 
Citation: Deng L, etal., J Cell Biochem. 2011 Apr;112(4):1046-54. doi: 10.1002/jcb.23017.
Pubmed: (View Article at PubMed) PMID:21308733
DOI: Full-text: DOI:10.1002/jcb.23017

Previous studies have demonstrated that transforming growth factor-beta3 (TGF-beta3) protected liver against fibrosis in vivo and vitro, but its regulation is poorly understood. In addition, the cAMP-responsive element (CRE) in TGF-beta3 promoter is recognized as an important regulatory site for TGF-beta3 auto-regulation. Thus, we hypothesize that transcription factor CRE-binding protein-1 (CREB-1) regulates the auto-induction of TGF-beta3 in hepatic stellate cells (HSCs). We used exogenous TGF-beta3 to activate the signal pathway of TGF-beta3 auto-regulation in HSCs, results indicated that exogenous TGF-beta3 could up-regulate the protein and mRNA expressions of TGF-beta3, 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-beta3 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-beta3 stimulation of TGF-beta3 mRNA and protein expressions in HSCs, whereas up-regulation of CREB-1 induced this stimulation. Our results indicate that exogenous TGF-beta3 up-regulates the activity of TGF-beta3 promoter by activating CREB-1, then induces the mRNA and protein expressions of TGF-beta3. Especially, p-CREB-1 is a critical transcription factor in mediating TGF-beta3 auto-induction.


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CRRD Object Information
CRRD ID: 10059386
Created: 2015-08-14
Species: All species
Last Modified: 2015-08-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.