P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells.
Purinergic Signal
; 12(4): 687-695, 2016 12.
Article
en En
| MEDLINE
| ID: mdl-27565965
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)-1α promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calcium-activated chloride secretion. Here, we report that HIF-1α 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-1α-dependent cyst growth. In conclusion, P2Y2R mediates ATP-dependent cyst growth and is transcriptionally regulated by HIF-1α. These findings provide further mechanistic evidence on how hypoxia promotes cyst growth.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quistes
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Células Epiteliales
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Receptores Purinérgicos P2Y2
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Túbulos Renales Proximales
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2016
Tipo del documento:
Article