Kraus A, Grampp S, Goppelt-Strübe M, Schreiber R, Kunzelmann K, Peters DJM, Leipziger J, Schley G, Schoedel J, Eckardt KU, Buchholz B (2016)
Publication Type: Journal article
Publication year: 2016
Book Volume: 12
Pages Range: 687-695
Journal Issue: 4
DOI: 10.1007/s11302-016-9532-5
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.
APA:
Kraus, A., Grampp, S., Goppelt-Strübe, M., Schreiber, R., Kunzelmann, K., Peters, D.J.M.,... Buchholz, B. (2016). P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells. Purinergic Signalling, 12(4), 687-695. https://doi.org/10.1007/s11302-016-9532-5
MLA:
Kraus, Andre, et al. "P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells." Purinergic Signalling 12.4 (2016): 687-695.
BibTeX: Download