{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:37:38Z","timestamp":1785875858785,"version":"3.56.0"},"reference-count":56,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:p> Mesangial cell (MC) proliferation is a key feature in the pathogenesis of a number of renal diseases. Peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) has attracted considerable attention for its effects on stimulating cell differentiation and on inducing cell cycle arrest. We previously showed that aldosterone (Aldo) stimulates MC proliferation via the phosphoinositide 3-kinase (PI3K)\/Akt signaling pathway, which was dependent on reactive oxygen species (ROS)-mediated epithelial growth factor receptor (EGFR) transactivation (Huang S, Zhang A, Ding G, and Chen R. Am J Physiol Renal Physiol 296: F1323\u2013F1333, 2009). In this study, we examined whether the PPAR\u03b3 agonist rosiglitazone inhibited Aldo-induced MC proliferation by modulating ROS-dependent EGFR intracellular signaling. Rosiglitazone at 1\u201310 \u03bcM dose dependently inhibited Aldo-induced MC proliferation of cultured mouse MCs. The inhibitory effect was blocked by the PPAR\u03b3 antagonist PD-68235, indicating that the rosiglitazone effect acted through PPAR\u03b3 activation. Rosiglitazone also arrested Aldo-induced cell cycle progression and suppressed expression of cyclins D1 and A. Moreover, rosiglitazone dose dependently blocked Aldo-induced ROS production, EGFR phosphorylation, and PI3K\/Akt activation. These results suggest that the PPAR\u03b3 agonist rosiglitazone may inhibit Aldo-induced MC proliferation directly, by affecting ROS\/EGFR\/PI3K\/Akt signaling pathways and cell cycle-regulatory proteins. PPAR\u03b3 might be a novel therapeutic target against glomerular diseases. <\/jats:p>","DOI":"10.1152\/ajprenal.00418.2010","type":"journal-article","created":{"date-parts":[[2010,12,2]],"date-time":"2010-12-02T05:49:53Z","timestamp":1291268993000},"page":"F393-F402","source":"Crossref","is-referenced-by-count":19,"title":["A PPAR\u03b3 agonist inhibits aldosterone-induced mesangial cell proliferation by blocking ROS-dependent EGFR intracellular signaling"],"prefix":"10.1152","volume":"300","author":[{"given":"Yanggang","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University and"},{"name":"Institute of Pediatrics, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University and"},{"name":"Institute of 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