title: TRPV4 channel inhibits TGF-β1-induced proliferation of hepatic stellate cells.
abstract: TRPV4, one of the TRP channels, is implicated in diverse physiological and pathological processes including cell proliferation. However, the role of TRPV4 in liver fibrosis is largely unknown. Here, we characterized the role of TRPV4 in regulating HSC-T6 cell proliferation. TRPV4 mRNA and protein were measured by RT-PCR and Western blot in patients and rat model of liver fibrosis in vivo and TGF-β1-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPV4 were dramatically increased in liver fibrotic tissues of both patients and CCl4-treated rats. Stimulation of HSC-T6 cells with TGF-β1 resulted in increase of TRPV4 mRNA and protein. However, TGF-β1-induced HSC-T6 cell proliferation was inhibited by Ruthenium Red (Ru) or synthetic siRNA targeting TRPV4, and this was accompanied by downregulation of myofibroblast markers including α-SMA and Col1α1. Moreover, our study revealed that miR-203 was downregulated in liver fibrotic tissues and TGF-β1-treated HSC-T6 cell. Bioinformatics analyses predict that TRPV4 is the potential target of miR-203. In addition, overexpression of miR-203 in TGF-β1-induced HSC significantly reduced TRPV4 expression, indicating TRPV4, which was regulated by miR-203, may function as a novel regulator to modulate TGF-β1-induced HSC-T6 proliferation.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China; The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhan
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Hefei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride