title: Inhibition of IRF3 expression reduces TGF-β1-induced proliferation of hepatic stellate cells.
abstract: Therapeutic management of liver fibrosis remains an unresolved clinical problem. Activation of hepatic stellate cell (HSC) is a pivotal event in the progression of liver fibrosis. Recent reports have showed that inhibition of activated HSC proliferation contributes to the reversal of liver fibrosis. Interferon regulatory factor 3 (IRF3), one member of the interferon regulatory factor (IRF) family, is recently proven to be a critical modulator in cardiac fibrosis. And accumulating evidence demonstrated that IRF3 plays a crucial role in liver diseases, such as hepatic steatosis, liver inflammation, and alcoholic liver injury. However, the understanding of the function of IRF3 in liver fibrosis remains limited. Our results identified the role of IRF3 in regulating human HSC (LX-2 cell) cell proliferation and apoptosis. The present study indicated that the expression of IRF3 was significantly increased in HSCs in response to TGF-β1 stimulation. Moreover, a stable and unlimited source of human HSC, the LX-2 cell line, transfected with IRF3-siRNA significantly decreases the expression level of type I collagen (Col1a1) and α-smooth muscle actin (α-SMA) in activated LX-2 cells. On the contrary, overexpression of IRF3 gives rise to an upregulation of Col1a1 and α-SMA in LX-2 cells, and further promoted HSC proliferation. Moreover, the inhibition of IRF3 significantly suppressed TGF-β1-induced HSC proliferation and increased its apoptosis. Of note, the present study indicated IRF3 may regulate LX-2 cell proliferation by via AKT signaling pathway. In summary, these observations suggest IRF3 may function as a novel regulator to modulate TGF-β1-induced LX-2 proliferation, at least in part, via AKT signaling pathway.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Ming-ming
authors.initials: MM
authors.lastname: Ni
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Ya-rui
authors.initials: YR
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Ying-hua
authors.initials: YH
authors.lastname: He
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China. ahmulijun001@163.com.|Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China. ahmulijun001@163.com.|School of Pharmacy, Anhui Medical University, 81 Mei Shan Road, Hefei, Anhui Province, 230032, China. ahmulijun001@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D055166:Hepatic Stellate Cells / Q000166:cytology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000502:physiology*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D053773:Transforming Growth Factor beta1
keywords: AKT; Hepatic stellate cell; IRF3; Liver fibrosis