title: Periostin down-regulation attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1.
abstract: Liver fibrosis is characterized by an exacerbated accumulation of deposition of the extracellular matrix (ECM), and the activation of hepatic stellate cells (HSC) plays a pivotal role in the development of liver fibrosis. Periostin has been shown to regulate cell adhesion, proliferation, migration and apoptosis; however, the involvement of periostin and its role in transforming growth factor (TGF)-β1-induced HSC activation remains unclear. We used RT-PCR and Western blot to evaluate the expression level of periostin in hepatic fibrosis tissues and HSCs, respectively. Cell proliferation was determined using the Cell Proliferation ELISA BrdU kit, cell cycle was analysed by flow cytometry. The expression of α-smooth muscle actin (α-SMA), collagen I, TGF-β1, p-Smad2 and p-Smad3 were determined by western blot. Our study found that periostin was up-regulated in liver fibrotic tissues and activated HSCs. In addition, siRNA-periostin suppressed TGF-β1-induced HSC proliferation. The HSC transfected with siRNA-periostin significantly inhibited TGF-β1-induced expression levels of α-SMA and collagen I. Furthermore, TGF-β1 stimulated the expression of periostin, and siRNA-periostin attenuated TGF-β1-induced Smad2/3 activation in HSCs. These results suggest that periostin may function as a novel regulator to modulate HSC activation, potentially by promoting the TGF-β1/Smad signalling pathway, and propose a strategy to target periostin for the treatment of liver fibrosis.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hong
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Shejiao
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fenrong
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Gang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lei
mesh_terms: D000199:Actins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D015536:Down-Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; C512835:POSTN protein, human; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1
keywords: TGF-β1; fibrosis; hepatic stellate cells; periostin