HIF-1α promotes cyst progression in a mouse model of autosomal dominant polycystic kidney disease

Kidney International
Andre KrausBjoern Buchholz

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by mutations of the PKD1 gene and characterized by growth of bilateral renal cysts. Cyst growth is accompanied by regional hypoxia and induction of hypoxia-inducible factor (HIF)-1α in cyst-lining epithelial cells. To determine the relevance of HIF-1α for cyst growth in vivo we used an inducible kidney epithelium-specific knockout mouse to delete Pkd1 at postnatal day 20 or 35 to induce polycystic kidney disease of different severity and analyzed the effects of Hif-1α co-deletion and HIF-1α stabilization using a prolyl-hydroxylase inhibitor. HIF-1α expression was enhanced in kidneys with progressive cyst growth induced by early Pkd1 deletion, but unchanged in the milder phenotype induced by later Pkd1 deletion. Hif-1α co-deletion significantly attenuated cyst growth in the severe, but not in the mild, phenotype. Application of a prolyl-hydroxylase inhibitor resulted in severe aggravation of the mild phenotype with rapid loss of renal function. HIF-1α expression was associated with induction of genes that mediate calcium-activated chloride secretion. Thus, HIF-1α does not seem to play a role in early cyst formation, but accelerates cyst growth during progressi...Continue Reading

Citations

May 27, 2020·Current Opinion in Nephrology and Hypertension·Yu KurataMasaomi Nangaku
Sep 7, 2019·Nature Reviews. Nephrology·Johannes Schödel, Peter J Ratcliffe
Aug 30, 2020·Nature Communications·Ines CabritaBjörn Buchholz
Jan 7, 2020·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Tetsuhiro Tanaka
Feb 10, 2020·Clinical and Experimental Nephrology·Yusuke UshioToshio Mochizuki
Sep 5, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wajima SafiBjoern Buchholz
Dec 2, 2020·International Journal of Molecular Sciences·Maria FragiadakiAlbert C M Ong
Nov 23, 2020·Nephrology·Desmond Y H YapUNKNOWN APSN HIF-PHI Recommendation Committee
Dec 8, 2020·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Harold M Aukema
Dec 15, 2019·Seminars in Nephrology·Marieta TheodorakopoulouPantelis Sarafidis
Mar 11, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jinzhao HeBaoxue Yang
Apr 23, 2020·Cellular Signalling·Chiara Formica, Dorien J M Peters
Mar 3, 2021·Journal of the American Society of Nephrology : JASN·Tadao AkizawaMichael Reusch
Mar 3, 2021·Journal of the American Society of Nephrology : JASN·Fei LiuJianhua Mao
Feb 26, 2021·Therapeutics and Clinical Risk Management·Taisuke IshiiMasaomi Nangaku
Sep 4, 2019·Advances in Chronic Kidney Disease·Neil S Sanghani, Volker H Haase
Mar 3, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Masaomi NangakuYasuhiro Komatsu
Mar 30, 2021·Clinical Kidney Journal·Steven Van Laecke, Wim Van Biesen
Apr 10, 2021·Journal of Physiology and Biochemistry·Ashish K SinghAnil K Pasupulati
Apr 26, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anna FaivreSophie de Seigneux
May 1, 2021·International Journal of Molecular Sciences·Cassandra Millet-BoureimaChiara Gamberi
Apr 30, 2021·Cell Calcium·Ines CabritaRainer Schreiber
Jul 3, 2021·International Journal of Molecular Sciences·Johannes LeiererGert Mayer
Jul 3, 2021·International Journal of Molecular Sciences·Khaoula TalbiKarl Kunzelmann
Jun 3, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jonathan BarrattChristophe Mariat
Sep 3, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Khaoula TalbiRainer Schreiber
Sep 7, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qin YaoValeriu Cebotaru
Jan 20, 2022·Antioxidants & Redox Signaling·Zuo-Lin LiBi-Cheng Liu

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