title: Septin4_i1 regulates apoptosis in hepatic stellate cells through peroxisome proliferator-activated receptor-γ/Akt/B-cell lymphoma 2 pathway.
abstract: Apoptosis of activated hepatic stellate cells (HSCs) has been verified as a potential mechanism to aid in hepatic fibrosis remission. Earlier research suggests that Septin4_i1 may sensitize hepatocellular carcinoma cells to serum starvation-induced apoptosis. Here, we aimed to investigate the effect of Septin4_i1 on HSC apoptosis and explore the associated signaling pathways. We found that Septin4_i1 can induce apoptosis in LX-2 cells and that this is accompanied by an up-regulation in cleaved-caspase-3 and peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and a down-regulation in α-SMA expression. Over-expression of Septin4_i1 reduced phosphorylated Akt and B-cell lymphoma 2 (Bcl-2) expression but had no effect on the expression of p53 and death receptor (DR)-5. The decreased expression of Bcl-2 and the increased expression of cleaved-caspase-3 induced by Sept4_i1 could be reversed by GW501516, a PPAR-β/δ agonist that has been reported by others to enhance Akt signaling. In addition, GW9662, an antagonist of PPAR-γ, could also inhibit apoptosis in LX-2 cells induced by Sept4_i1. In conclusion, our data suggest that Sept4_i1 induces HSC apoptosis by inhibiting Akt and Bcl-2 expression and up-regulating PPAR-γ expression.
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, People's Republic of China (JW)
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Jinling
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Yinong
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Tianhua
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Xingxin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, People's Republic of China (DZ, JW, XS, JC, YD, JP, TX, YQ, XH, CH)
authors.forename: Caiqun
authors.initials: C
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D058112:Septins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000595707:BCL2 protein, human; D047495:PPAR gamma; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D051057:Proto-Oncogene Proteins c-akt; C492027:SEPTIN4 protein, human; D058112:Septins
keywords: Apoptosis; Hepatic fibrosis; Hepatic stellate cells; Septin4_i1