{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:45:38Z","timestamp":1791121538001,"version":"4.1.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:p>Cyst expansion in polycystic kidney disease (PKD) results in localized hypoxia in the kidney that may activate hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1). HIF-1\u03b1 and autophagy, a form of programmed cell repair, are induced by hypoxia. The purposes were to determine HIF-1\u03b1 expression and autophagy in rat and mouse models of PKD. HIF-1\u03b1 was detected by electrochemiluminescence. Autophagy was visualized by electron microscopy (EM). LC3 and beclin-1, markers of autophagy, were detected by immunoblotting. Eight-week-old male heterozygous (Cy\/+) and 4-wk-old homozygous (Cy\/Cy) Han:SPRD rats, 4-wk-old cpk mice, and 112-day-old Pkd2WS25\/\u2212 mice with a mutation in the Pkd2 gene were studied. HIF-1\u03b1 was significantly increased in massive Cy\/Cy and cpk kidneys and not smaller Cy\/+ and Pkd2WS25\/\u2212 kidneys. On EM, features of autophagy were seen in wild-type (+\/+), Cy\/+, and cpk kidneys: autophagosomes, mitophagy, and autolysosomes. Specifically, autophagosomes were found on EM in the tubular cells lining the cysts in cpk mice. The increase in LC3-II, a marker of autophagosome production and beclin, a regulator of autophagy, in Cy\/Cy and cpk kidneys, followed the same pattern of increase as HIF-1\u03b1. To determine the role of HIF-1\u03b1 in cyst formation and\/or growth, Cy\/+ rats, Cy\/Cy rats, and cpk mice were treated with the HIF-1\u03b1 inhibitor 2-methoxyestradiol (2ME2). 2ME2 had no significant effect on kidney volume or cyst volume density. In summary, HIF-1\u03b1 is highly expressed in the late stages of PKD and is associated with an increase in LC3-II and beclin-1. The first demonstration of autophagosomes in PKD kidneys is reported. Inhibition of HIF-1\u03b1 did not have a therapeutic effect.<\/jats:p>","DOI":"10.1152\/ajprenal.00348.2010","type":"journal-article","created":{"date-parts":[[2011,1,26]],"date-time":"2011-01-26T20:35:58Z","timestamp":1296074158000},"page":"F1235-F1243","source":"Crossref","is-referenced-by-count":109,"title":["Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and autophagy in polycystic kidney disease (PKD)"],"prefix":"10.1152","volume":"300","author":[{"given":"Franck","family":"Belibi","sequence":"first","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iram","family":"Zafar","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado; 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