{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:43:04Z","timestamp":1789418584533,"version":"build-2803163510"},"reference-count":58,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p>Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy\/Cy kidneys and normal (+\/+) kidneys at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5-fold expression changes compared with age-matched +\/+ kidneys for canonical pathway analysis. We found nine pathways in common between 3- and 7-day Cy\/Cy kidneys. Three significantly changed pathways were designated \u201cVitamin D Receptor (VDR)\/Retinoid X Receptor (RXR) Activation,\u201d \u201cLPS\/IL-1-Mediated Inhibition of RXR Function,\u201d and \u201cLiver X Receptor (LXR)\/RXR Activation.\u201d These results suggest that RXR-mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the upregulation of Ptx2, Alox15b, OSP, and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy\/Cy kidneys compared with 3-day +\/+ kidneys. The increased RXR protein was observed in both the nucleus and cytoplasm of cystic epithelial cells in early-stage Cy\/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR-mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.<\/jats:p>","DOI":"10.1152\/ajprenal.00470.2010","type":"journal-article","created":{"date-parts":[[2010,10,7]],"date-time":"2010-10-07T02:33:59Z","timestamp":1286418839000},"page":"F177-F188","source":"Crossref","is-referenced-by-count":16,"title":["Global gene expression profiling in early-stage polycystic kidney disease in the Han:SPRD Cy rat identifies a role for RXR signaling"],"prefix":"10.1152","volume":"300","author":[{"given":"Masanori","family":"Kugita","sequence":"first","affiliation":[{"name":"Education and Research Center of Animal Models for Human Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Nishii","sequence":"additional","affiliation":[{"name":"Faculty of 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