{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:43:17Z","timestamp":1772754197646,"version":"3.50.1"},"reference-count":33,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Hepatic stellate cells (HSCs) are liver-specific pericytes with capabilities to recruit to vessels and secret pro-angiogenic cytokines and thus actively involved in pathologic vascularization during liver fibrosis. Peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) is a switch molecule controlling HSC activation. Herein we investigated the PPAR\u03b3 regulation of angiogenic signal transduction and the molecular mechanisms in HSCs. Primary rat HSCs and liver sinusoidal endothelial cells (LSECs) were isolated and used in this study. Using Boyden chamber assay and tubulogenesis assay, we found that focal adhesion kinase (FAK)\/RhoA signaling activated by platelet-derived growth factor (PDGF) was required for HSC motility and associated vascularization. PDGF also simulated vascular endothelial growth factor (VEGF) expression and HSC-driven vascularization via signals mediated by extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Gain- and loss-of-function analyses demonstrated that activation of PPAR\u03b3 interrupted FAK\/RhoA, ERK and mTOR cascades and inhibited HSC-based vascularization. Molecular evidence further revealed that PPAR\u03b3 attenuation of HSC angiogenic properties was dependent on inhibition of PDGF-\u03b2 receptor expression. We concluded that PPAR\u03b3 inhibited angiogenic signal transduction via transrepression of PDGF-\u03b2 receptor leading to inhibited HSC motility, reduced VEGF expression, and thereby attenuated HSC-driven angiogenesis. PPAR\u03b3 could be a molecular target for preventing vascular remolding in hepatic fibrosis.<\/jats:p>","DOI":"10.1242\/jcs.128306","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T01:58:57Z","timestamp":1384999137000},"source":"Crossref","is-referenced-by-count":16,"title":["Peroxisome proliferator-activated receptor-\u03b3 interrupts angiogenic signal transduction via transrepression of platelet-derived growth factor-\u03b2 receptor in hepatic stellate cells"],"prefix":"10.1242","author":[{"given":"Feng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desong","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naqi","family":"Lian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2021042613361909200_b1","doi-asserted-by":"publisher","first-page":"G210","DOI":"10.1152\/ajpgi.00047.2010","article-title":"Mammalian target of rapamycin mediates the angiogenic effects of leptin in human hepatic stellate cells.","volume":"301","author":"Aleffi","year":"2011","journal-title":"Am. 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