机构：[1]Department of Clinical Laboratory, Kunshan First People’s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu Province 215300, China[2]Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China[3]Department of Liver Surgery,The First Affiliated Hospital of Nanjing Medical University, Nanjing, China江苏省人民医院
Background and Aims. Accumulating evidence reveals that PPAR gamma plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPAR gamma in hypoxia-induced hepatic fibrogenesis and its possible mechanism. Methods. Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPAR gamma agonist rosiglitazone. Liver sections were stained with HE and Sirius red staining 8 weeks later. HSCs were exposed to hypoxic environment in the presence or absence of rosiglitazone, and expression of PPAR gamma and two fibrosis markers, alpha-SMA and desmin, were measured using western blot and immunofluorescence staining. Next, levels of PPAR gamma, alpha-SMA, and desmin as well as PKG and cGMP activity were detected using PI3K/AKT and a cGMP activator or inhibitor. Results. Hypoxia promoted the induction and progress of hepatic fibrosis and HSCs activation. Meanwhile, rosiglitazone significantly antagonized the effects induced by hypoxia. Signaling by sGC/cGMP/PKG promoted the inhibitory effect of PPAR gamma on hypoxia-induced activation of HSCs. Moreover, PI3K/AKT signaling or PDE5 blocked the above response of PPAR gamma. Conclusion. sGC/cGMP/PKG and PI3K/AKT signals act on PPAR gamma synergistically to attenuate hypoxia-induced HSC activation.
基金：
Shanghai Science and Technology Commission Foundation [16411972700]
第一作者机构：[1]Department of Clinical Laboratory, Kunshan First People’s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu Province 215300, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhang Qinghui,Xiang Shihao,Liu Qingqian,et al.PPAR gamma Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling[J].PPAR RESEARCH.2018,2018:doi:10.1155/2018/6970407.
APA：
Zhang, Qinghui,Xiang, Shihao,Liu, Qingqian,Gu, Tao,Yao, Yongliang&Lu, Xiaojie.(2018).PPAR gamma Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling.PPAR RESEARCH,2018,
MLA：
Zhang, Qinghui,et al."PPAR gamma Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling".PPAR RESEARCH 2018.(2018)
