PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3KAKT and cGMPPKG Signaling
Joint Authors
Yao, Yongliang
Lu, Xiao-Jie
Zhang, Qinghui
Xiang, Shihao
Liu, Qingqian
Gu, Tao
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-03-01
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Background and Aims.
Accumulating evidence reveals that PPARγ 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 PPARγ 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 PPARγ 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 PPARγ and two fibrosis markers, α-SMA and desmin, were measured using western blot and immunofluorescence staining.
Next, levels of PPARγ, α-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 PPARγ on hypoxia-induced activation of HSCs.
Moreover, PI3K/AKT signaling or PDE5 blocked the above response of PPARγ.
Conclusion.
sGC/cGMP/PKG and PI3K/AKT signals act on PPARγ synergistically to attenuate hypoxia-induced HSC activation.
American Psychological Association (APA)
Zhang, Qinghui& Xiang, Shihao& Liu, Qingqian& Gu, Tao& Yao, Yongliang& Lu, Xiao-Jie. 2018. PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3KAKT and cGMPPKG Signaling. PPAR Research،Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1212526
Modern Language Association (MLA)
Zhang, Qinghui…[et al.]. PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3KAKT and cGMPPKG Signaling. PPAR Research No. 2018 (2018), pp.1-10.
https://search.emarefa.net/detail/BIM-1212526
American Medical Association (AMA)
Zhang, Qinghui& Xiang, Shihao& Liu, Qingqian& Gu, Tao& Yao, Yongliang& Lu, Xiao-Jie. PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3KAKT and cGMPPKG Signaling. PPAR Research. 2018. Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1212526
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1212526