title: Liganded Vitamin D Receptor Through Its Interacting Repressor Inhibits the Expression of Type I Collagen α1.
abstract: Hepatic fibrosis is a reversible process involving plenty of transcription factors and pathways. Vitamin D receptor (VDR) as a member of ligand-induced transcription factors can interact with 9-cis retinoid X receptor (RXR) and VDR-interacting repressor (VDIR) to mediate transactivation or transrepression in the absence or in the presence of VDR ligand to regulate the expression of VDR target genes. The active form of vitamin D [1α,25(OH)2D3] can downregulate the expression of type I collagen both α1 and α2 (COLIα1 and COLIα2) in hepatic stellate cells (HSC-T6) in a time-dependent fashion, which provides a new direction for hepatic fibrosis therapy. As one of VDR target genes, rat COLIα1 gene contains 1αnVDRE (E-box1 and E-box2) in its promoter, and unliganded VDR/RXR may bind to 1αnVDRE through VDIR to mediate transactivation, whereas liganded VDR/RXR may bind to 1αnVDRE through VDIR for transrepression. The results suggested a sort of relying on each other relationship between VDR/RXR and VDIR in regulating the expression of COLIα1 gene in HSC-T6 cells, which established VDR as a potential target for blocking and even reversing hepatic fibrosis.
authors.affiliation: 1 The Institute of Cell Therapy, China Three Gorges University , Yichang, China .|2 The First People's Hospital of Yichang , Hubei, China .|3 Medical College, China Three Gorges University , Yichang, China .|4 Institute of Liver Diseases, China Three Gorges University , Yichang, China .|5 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University , Yichang, China .
authors.forename: Lin-Yan
authors.initials: LY
authors.lastname: Wan
authors.affiliation: 3 Medical College, China Three Gorges University , Yichang, China .
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: 1 The Institute of Cell Therapy, China Three Gorges University , Yichang, China .|2 The First People's Hospital of Yichang , Hubei, China .
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Li
authors.affiliation: 6 First Clinical Medical College, China Three Gorges University , Yichang, China .
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Tang
authors.affiliation: 3 Medical College, China Three Gorges University , Yichang, China .|5 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University , Yichang, China .
authors.forename: Meng-Di
authors.initials: MD
authors.lastname: Chen
authors.affiliation: 3 Medical College, China Three Gorges University , Yichang, China .
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Ni
authors.affiliation: 3 Medical College, China Three Gorges University , Yichang, China .
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: 1 The Institute of Cell Therapy, China Three Gorges University , Yichang, China .|2 The First People's Hospital of Yichang , Hubei, China .|3 Medical College, China Three Gorges University , Yichang, China .|4 Institute of Liver Diseases, China Three Gorges University , Yichang, China .|5 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University , Yichang, China .
authors.forename: Chang-Bai
authors.initials: CB
authors.lastname: Liu
authors.affiliation: 1 The Institute of Cell Therapy, China Three Gorges University , Yichang, China .|2 The First People's Hospital of Yichang , Hubei, China .|3 Medical College, China Three Gorges University , Yichang, China .|4 Institute of Liver Diseases, China Three Gorges University , Yichang, China .|5 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University , Yichang, China .
authors.forename: Jiang-Feng
authors.initials: JF
authors.lastname: Wu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism*; D008024:Ligands; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014807:Vitamin D / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D008024:Ligands; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D014807:Vitamin D