title: Knockdown of HIPK2 attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1.
abstract: Homeodomain-interacting protein kinase 2 (HIPK2), a member of HIPKs family, is considered as a key regulator in fibrosis. However, the roles of HIPK2 in hepatic stellate cells (HSCs) activation and liver fibrosis are still unclear. Therefore, in this study, we investigated the roles of HIPK2 in HSCs activation and liver fibrosis. Our results showed that HIPK2 expression was significantly up-regulated in liver fibrotic tissues and TGF-β1-treated HSCs. Knockdown of HIPK2 significantly inhibited TGF-β1-induced HSCs proliferation, as well as decreased the expression levels of α-SMA and collagen I. Furthermore, knockdown of HIPK2 attenuated the phosphorylation of Smad3 in the presence of TGF-β1. In conclusion, these results demonstrated that HIPK2 may function as a novel regulator to modulate HSC activation, potentially by inhibiting the TGF-β1/Smad3 signaling pathway. The results provide supporting evidence that HIPK2 may be a potential target for the treatment of liver fibrosis.
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
authors.forename: Zu-Jiang
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China. Electronic address: changyu467sun@163.com.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Jiao
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Jiang
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D055785:Gene Knockdown Techniques; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D053773:Transforming Growth Factor beta1; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Hepatic stellate cells (HSCs); Homeodomain-interacting protein kinase 2 (HIPK2); Liver fibrosis; TGF-β1/Smad pathway