{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:46:05Z","timestamp":1778888765155,"version":"3.51.4"},"reference-count":54,"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>In autosomal recessive polycystic kidney disease (ARPKD), progressive enlargement of fluid-filled cysts is due to aberrant proliferation of tubule epithelial cells and transepithelial fluid secretion leading to extensive nephron loss and interstitial fibrosis. Congenital hepatic fibrosis associated with biliary cysts\/dilatations is the most common extrarenal manifestation in ARPKD and can lead to massive liver enlargement. Peroxisome proliferator-activated receptor \u03b3 (PPAR-\u03b3), a member of the ligand-dependent nuclear receptor superfamily, is expressed in a variety of tissues, including the kidneys and liver, and plays important roles in cell proliferation, fibrosis, and inflammation. In the current study, we determined that pioglitazone (PIO), a PPAR-\u03b3 agonist, decreases polycystic kidney and liver disease progression in the polycystic kidney rat, an orthologous model of human ARPKD. Daily treatment with 10 mg\/kg PIO for 16 wk decreased kidney weight (% of body weight), renal cystic area, serum urea nitrogen, and the number of Ki67-, pERK1\/2-, and pS6-positive cells in the kidney. There was also a decrease in liver weight (% of body weight), liver cystic area, fibrotic index, and the number of Ki67-, pERK1\/2-, pERK5-, and TGF-\u03b2-positive cells in the liver. Taken together, these data suggest that PIO inhibits the progression of polycystic kidney and liver disease in a model of human ARPKD by inhibiting cell proliferation and fibrosis. These findings suggest that PPAR-\u03b3 agonists may have therapeutic value in the treatment of the renal and hepatic manifestations of ARPKD.<\/jats:p>","DOI":"10.1152\/ajprenal.00460.2010","type":"journal-article","created":{"date-parts":[[2010,12,9]],"date-time":"2010-12-09T01:47:16Z","timestamp":1291859236000},"page":"F465-F474","source":"Crossref","is-referenced-by-count":77,"title":["PPAR-\u03b3 agonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease"],"prefix":"10.1152","volume":"300","author":[{"given":"Daisuke","family":"Yoshihara","sequence":"first","affiliation":[{"name":"Education and Research Center of Animal Models for Human Diseases,"},{"name":"Division of Molecular Genetics, Institute for Comprehensive Medical Science,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kurahashi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Institute 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