title: Suppression of hepatic stellate cell activation through downregulation of gremlin1 expression by the miR-23b/27b cluster.
abstract: The imbalance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways is a critical step in promoting hepatic stellate cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance. Something remains unclear about the regulatory mechanisms of gremlin1 action on hepatic stellate cell activation and hepatic fibrosis. In the current study, gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown of gremlin1 with siRNAs suppresses hepatic stellate cell activation and attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b cluster members bind to 3'-untranslated region of gremlin1 resulting in reduction of transforming growth factor β, α-smooth muscle actin and collagenI α1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic stellate cell activation and hepatic fibrogenesis through impairment of the balance between transforming growth factor β and bone morphogenetic protein 7 signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic stellate cells through binding gremlin1 to rectify the imbalance.
authors.affiliation: The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China.|Medical College, China Three Gorges University, Yichang, 443002, China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
authors.forename: Xian-Yi
authors.initials: XY
authors.lastname: Zeng
authors.affiliation: Medical College, China Three Gorges University, Yichang, 443002, China.|Institute of Liver Diseases, China Three Gorges University, Yichang, 443002, China.
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Medical College, China Three Gorges University, Yichang, 443002, China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: He
authors.affiliation: The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China.|Medical College, China Three Gorges University, Yichang, 443002, China.|The First People's Hospital of Yichang, Hubei Yichang, 443000, China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.|Institute of Liver Diseases, China Three Gorges University, Yichang, 443002, China.
authors.forename: Lin-Yan
authors.initials: LY
authors.lastname: Wan
authors.affiliation: The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China.|Medical College, China Three Gorges University, Yichang, 443002, China.|The First People's Hospital of Yichang, Hubei Yichang, 443000, China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Medical College, China Three Gorges University, Yichang, 443002, China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Ni
authors.affiliation: Medical College, China Three Gorges University, Yichang, 443002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China.|Medical College, China Three Gorges University, Yichang, 443002, China.|The First People's Hospital of Yichang, Hubei Yichang, 443000, China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.|Institute of Liver Diseases, China Three Gorges University, Yichang, 443002, China.
authors.forename: Jiang-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: The Institute of Cell Therapy, China Three Gorges University, Yichang, 443000, China.|Medical College, China Three Gorges University, Yichang, 443002, China.|The First People's Hospital of Yichang, Hubei Yichang, 443000, China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.|Institute of Liver Diseases, China Three Gorges University, Yichang, 443002, China.
authors.forename: Chang-Bai
authors.initials: CB
authors.lastname: Liu
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology; D016207:Cytokines; D015536:Down-Regulation; D055166:Hepatic Stellate Cells / Q000502:physiology*; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D055419:Bone Morphogenetic Protein 7; D016207:Cytokines; D035683:MicroRNAs; D011506:Proteins; D016212:Transforming Growth Factor beta; C107276:Grem1 protein, rat; C000590974:MIRN23a microRNA, rat; C000594049:MIRN27 microRNA, rat
keywords: BMP-7; TGF-β; hepatic fibrosis; miR-23b/27b cluster; siRNA