{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:49:39Z","timestamp":1787669379973,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["16411972700"],"award-info":[{"award-number":["16411972700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PPAR Research"],"published-print":{"date-parts":[[2018]]},"abstract":"<jats:p><jats:italic>Background and Aims<\/jats:italic>. Accumulating evidence reveals that PPAR<jats:italic>\u03b3<\/jats:italic> 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<jats:italic>\u03b3<\/jats:italic> in hypoxia-induced hepatic fibrogenesis and its possible mechanism.<jats:italic> Methods<\/jats:italic>. 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<jats:italic>\u03b3<\/jats:italic> 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<jats:italic>\u03b3<\/jats:italic> and two fibrosis markers, <jats:italic>\u03b1<\/jats:italic>-SMA and desmin, were measured using western blot and immunofluorescence staining. Next, levels of PPAR<jats:italic>\u03b3<\/jats:italic>, <jats:italic>\u03b1<\/jats:italic>-SMA, and desmin as well as PKG and cGMP activity were detected using PI3K\/AKT and a cGMP activator or inhibitor.<jats:italic> Results<\/jats:italic>. 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<jats:italic>\u03b3<\/jats:italic> on hypoxia-induced activation of HSCs. Moreover, PI3K\/AKT signaling or PDE5 blocked the above response of PPAR<jats:italic>\u03b3<\/jats:italic>.<jats:italic> Conclusion<\/jats:italic>. sGC\/cGMP\/PKG and PI3K\/AKT signals act on PPAR<jats:italic>\u03b3<\/jats:italic> synergistically to attenuate hypoxia-induced HSC activation.<\/jats:p>","DOI":"10.1155\/2018\/6970407","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T18:34:18Z","timestamp":1519929258000},"page":"1-10","source":"Crossref","is-referenced-by-count":22,"title":["PPAR<i>\u03b3<\/i> Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K\/AKT and cGMP\/PKG Signaling"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2164-6452","authenticated-orcid":true,"given":"Qinghui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Kunshan First People\u2019s Hospital, Affiliated to Jiangsu University, Kunshan, Jiangsu 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