Kraus, Andre and Grampp, Steffen and Goppelt-Struebe, Margarete and Schreiber, Rainer and Kunzelmann, Karl and Peters, Dorien J. M. and Leipziger, Jens and Schley, Gunnar and Schoedel, Johannes and Eckardt, Kai-Uwe and Buchholz, Bjoern (2016) P2Y2R is a direct target of HIF-1 alpha and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells. Purinergic Signalling, 12 (4). pp. 687-695. ISSN 1573-9538, 1573-9546
Full text not available from this repository. (Request a copy)Abstract
Polycystic kidney diseases are characterized by numerous renal cysts that continuously enlarge resulting in compression of intact nephrons and tissue hypoxia. Recently, we have shown that hypoxia-inducible factor (HIF)-1 alpha promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calcium-activated chloride secretion. Here, we report that HIF-1 alpha directly activates expression of the purinergic receptor P2Y2R in human primary renal tubular cells. In addition, we found that P2Y2R is highly expressed in cyst-lining cells of human ADPKD kidneys as well as PKD1 orthologous mouse kidneys. Knockdown of P2Y2R in renal collecting duct cells inhibited calcium-dependent chloride secretion in Ussing chamber analyses. In line with these findings, knockdown of P2Y2R retarded cyst expansion in vitro and prevented ATP- and HIF-1 alpha-dependent cyst growth. In conclusion, P2Y2R mediates ATP-dependent cyst growth and is transcriptionally regulated by HIF-1 alpha. These findings provide further mechanistic evidence on how hypoxia promotes cyst growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLYCYSTIC KIDNEY-DISEASE; ACTIVATED CHLORIDE SECRETION; IN-VITRO; LUMINAL P2Y(2); HYPOXIA; RECEPTORS; PROLIFERATION; INHIBITION; HIF; ATP; Polycystic kidney disease; Cyst growth; Chloride secretion; ATP; P2Y2R; Hypoxia; HIF-1 alpha |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Apr 2019 12:33 |
| Last Modified: | 10 Apr 2019 12:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3893 |
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