Chromogranin A regulates renal function by triggering Weibel-Palade body exocytosis
2009 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, Vol. 20, no 7, 1623-1632 p.Article in journal (Refereed) Published
Chromogranin A (CHGA), a protein released from secretory granules of chromaffin cells and sympathetic nerves, triggers endothelin-1 release from endothelial cells. CHGA polymorphisms associate with an increased risk for ESRD, but whether altered CHGA-endothelium interactions may explain this association is unknown. Here, CHGA led to the release of endothelin-1 and Weibel-Palade body exocytosis in cultured human umbilical vein endothelial cells. In addition, CHGA triggered secretion of endothelin-1 from glomerular endothelial cells and TGF-beta1 from mesangial cells cocultured with glomerular endothelial cells. In humans, plasma CHGA correlated positively with endothelin-1 and negatively with GFR. GFR was highly heritable in twin pairs, and common promoter haplotypes of CHGA predicted GFR. In patients with progressive hypertensive renal disease, a CHGA haplotype predicted rate of GFR decline. In conclusion, these data suggest that CHGA acts through the glomerular endothelium to regulate renal function.
Place, publisher, year, edition, pages
2009. Vol. 20, no 7, 1623-1632 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-124355DOI: 10.1681/ASN.2008111148ISI: 000267775400027PubMedID: 19520754OAI: oai:DiVA.org:uu-124355DiVA: diva2:317380