title: Hypoxia induces peroxisome proliferator-activated receptor γ expression via HIF-1-dependent mechanisms in HepG2 cell line.
abstract: Hypoxia-inducible factor-1 (HIF-1) can activate expression of a broad range of genes in response to hypoxia. It has been shown that the levels of peroxisome proliferator-activated receptor γ (PPARγ) are influenced by changes in oxygen tension, and PPARγ plays a critical role in metabolism regulation and cancers. In this research, we observed an increased PPARγ mRNA and protein levels in company with increased HIF-1 protein levels in HepG2 cells in hypoxia as compared with in normoxia. Enforced expression of HIF-1α induced PPARγ1 and PPARγ2 expression, while knockdown of HIF-1α by small interference RNA deduced PPARγ1 and PPARγ2 expression in HepG2 cells under hypoxic conditions. By dual-luciferase reporter assay and chromatin immunoprecipitation assay we confirmed a functional hypoxic response element (HRE) localized at 684bp upstream of the transcriptional start site (TSS) of PPARγ1 and a functional HRE localized at 204bp downstream of the TSS of PPARγ2 in HepG2 cells. Additionally we observed an increase and co-presence of PPARγ and HIF-1α, and a highly positive correlation between PPARγ expression and HIF-1α expression (r=0.553, p<0.0001), in the same tumor tissue areas of hepatocellular carcinoma patients. Our data suggested a new mechanism of hepatocellular carcinoma cells response to hypoxia.
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ying-Ze
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Guo-Min
authors.initials: GM
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ming-Tai
authors.initials: MT
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hua-Lu
authors.initials: HL
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: junwu_zhang@pumc.edu.cn.
authors.forename: Jun-Wu
authors.initials: JW
authors.lastname: Zhang
mesh_terms: D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D015854:Up-Regulation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047495:PPAR gamma
keywords: HepG2 cell line; Human hepatocellular carcinoma; Hypoxia; Hypoxia-inducible factor-1; Peroxisome proliferator-activated receptor γ