Targeted vitamin D receptor expression in juxtaglomerular cells suppresses renin expression independent of parathyroid hormone and calcium.
Previously, we showed that vitamin D receptor gene knockout leads to hyperreninemia independent of calcium metabolism; however, the contribution of parathyroid hormone to renin upregulation remained unclear. Here we separated the role of vitamin D and parathyroid hormone in the regulation of renin expression in vivo by generating transgenic mice that overexpressed the human vitamin D receptor in renin-producing cells using the 4.1 kb Ren-1c gene promoter. Targeting of human vitamin D receptor to the juxtaglomerular cells of the mice was confirmed by immunohistochemistry. Renal renin mRNA levels and plasma renin activity were decreased in these transgenic mice by about 50% and 30%, respectively, with no significant change in blood pressure, calcium, or parathyroid hormone levels. Moreover using vitamin D receptor knockout mice, we found that expression of the human receptor in their juxtaglomerular cells reduced renin expression in these mice without affecting calcium or parathyroid hormone status. Our study shows that suppression of renin expression by 1,25-dihydroxyvitamin D in vivo is independent of parathyroid hormone and calcium.
Kong
Juan
J
Department of Medicine, Division of Biological Sciences, Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois 60637, USA.
Qiao
Guilin
G
Zhang
Zhongyi
Z
Liu
Shu Q
SQ
Li
Yan Chun
YC
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010281:Parathyroid Hormone / Q000502:physiology; D012333:RNA, Messenger / Q000097:blood; D018167:Receptors, Calcitriol / Q000235:genetics*; D012083:Renin / Q000235:genetics*
C470125:PTH protein, human; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D012083:Renin; D002117:Calcitriol; D002118:Calcium