PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling
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. R...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2018/6970407 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556514260287488 |
|---|---|
| author | Qinghui Zhang Shihao Xiang Qingqian Liu Tao Gu Yongliang Yao Xiaojie Lu |
| author_facet | Qinghui Zhang Shihao Xiang Qingqian Liu Tao Gu Yongliang Yao Xiaojie Lu |
| author_sort | Qinghui Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f465da453d9142e693005736c1f5b1e9 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-f465da453d9142e693005736c1f5b1e92025-02-03T05:45:15ZengWileyPPAR Research1687-47571687-47652018-01-01201810.1155/2018/69704076970407PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG SignalingQinghui Zhang0Shihao Xiang1Qingqian Liu2Tao Gu3Yongliang Yao4Xiaojie Lu5Department of Clinical Laboratory, Kunshan First People’s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu Province 215300, ChinaDepartment of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, ChinaDepartment of Clinical Laboratory, Kunshan First People’s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu Province 215300, ChinaDepartment of Clinical Laboratory, Kunshan First People’s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu Province 215300, ChinaDepartment of Clinical Laboratory, Kunshan First People’s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu Province 215300, ChinaDepartment of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackground 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.http://dx.doi.org/10.1155/2018/6970407 |
| spellingShingle | Qinghui Zhang Shihao Xiang Qingqian Liu Tao Gu Yongliang Yao Xiaojie Lu PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling PPAR Research |
| title | PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling |
| title_full | PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling |
| title_fullStr | PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling |
| title_full_unstemmed | PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling |
| title_short | PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling |
| title_sort | pparγ antagonizes hypoxia induced activation of hepatic stellate cell through cross mediating pi3k akt and cgmp pkg signaling |
| url | http://dx.doi.org/10.1155/2018/6970407 |
| work_keys_str_mv | AT qinghuizhang ppargantagonizeshypoxiainducedactivationofhepaticstellatecellthroughcrossmediatingpi3kaktandcgmppkgsignaling AT shihaoxiang ppargantagonizeshypoxiainducedactivationofhepaticstellatecellthroughcrossmediatingpi3kaktandcgmppkgsignaling AT qingqianliu ppargantagonizeshypoxiainducedactivationofhepaticstellatecellthroughcrossmediatingpi3kaktandcgmppkgsignaling AT taogu ppargantagonizeshypoxiainducedactivationofhepaticstellatecellthroughcrossmediatingpi3kaktandcgmppkgsignaling AT yongliangyao ppargantagonizeshypoxiainducedactivationofhepaticstellatecellthroughcrossmediatingpi3kaktandcgmppkgsignaling AT xiaojielu ppargantagonizeshypoxiainducedactivationofhepaticstellatecellthroughcrossmediatingpi3kaktandcgmppkgsignaling |