title: Effects of p-CREB-1 on transforming growth factor-β3 auto-regulation in hepatic stellate cells.
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.
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, 430022, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Deng
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jin Ming
authors.initials: JM
authors.lastname: Huang
authors.forename: Guan yu
authors.initials: Gy
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Ke shu
authors.initials: Ks
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D053782:Transforming Growth Factor beta3