Chromogranin A regulates renal function by triggering Weibel-Palade body exocytosis.
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.
Chen
Yuqing
Y
Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0838, USA.
Mahata
Manjula
M
Rao
Fangwen
F
Khandrika
Srikrishna
S
Courel
Maite
M
Fung
Maple M
MM
Zhang
Kuixing
K
Stridsberg
Mats
M
Ziegler
Michael G
MG
Hamilton
Bruce A
BA
Lipkowitz
Michael S
MS
Taupenot
Laurent
L
Nievergelt
Caroline
C
Mahata
Sushil K
SK
O'Connor
Daniel T
DT
D000818:Animals; D002478:Cells, Cultured; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002908:Chronic Disease; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020302:Weibel-Palade Bodies / Q000378:metabolism*
C506150:CHGA protein, human; D053379:Chromogranin A; D016232:Endothelins; D053773:Transforming Growth Factor beta1