Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway.
During metanephric kidney development, renin expression in the renal vasculature begins in larger vessels, shifting to smaller vessels and finally remaining restricted to the terminal portions of afferent arterioles at the entrance into the glomerular capillary network. The mechanisms determining the successive expression of renin along the vascular axis of the kidney are not well understood. Since the cAMP signaling cascade plays a central role in the regulation of both renin secretion and synthesis in the adult kidney, it seemed feasible that this pathway might also be critical for renin expression during kidney development. In the present study we determined the spatiotemporal development of renin expression and the development of the preglomerular arterial tree in mouse kidneys with renin cell-specific deletion of G(s)alpha, a core element for receptor activation of adenylyl cyclases. We found that in the absence of the G(s)alpha protein, renin expression was largely absent in the kidneys at any developmental stage, accompanied by alterations in the development of the preglomerular arterial tree. These data indicate that the maintenance of renin expression following a specific spatiotemporal pattern along the preglomerular vasculature critically depends on the availability of G(s)alpha. We infer from our data that the cAMP signaling pathway is not only critical for the regulation of renin synthesis and secretion in the mature kidney but that it also is critical for establishing the juxtaglomerular expression site of renin during development.
Neubauer
Björn
B
Department of Physiology, Universität Regensburg, Regensburg, Germany.
Machura
Katharina
K
Chen
Min
M
Weinstein
Lee S
LS
Oppermann
Mona
M
Sequeira-Lopez
Maria Luisa
ML
Gomez
R Ariel
RA
Schnermann
Jürgen
J
Castrop
Hayo
H
Kurtz
Armin
A
Wagner
Charlotte
C
D000818:Animals; D001160:Arterioles / Q000196:embryology / Q000502:physiology; D002864:Chromogranins; D000242:Cyclic AMP / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007606:Juxtaglomerular Apparatus / Q000196:embryology / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000196:embryology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012079:Renal Circulation / Q000502:physiology*; D012083:Renin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D002864:Chromogranins; D000242:Cyclic AMP; D012083:Renin; C498642:Gnas protein, mouse; D019205:GTP-Binding Protein alpha Subunits, Gs