Journal
HYPERTENSION
Volume 70, Issue 1, Pages 119-128Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.117.09283
Keywords
kidney; mice; mutation; phenotype; renin; angiotensin system
Categories
Funding
- National Institutes of Health [R37 HL-066242, RO1 HL-096735, RO1 DK-091330, P50 DK096373]
Ask authors/readers for more resources
Experimental or spontaneous genomic mutations of the renin-angiotensin system or its pharmacological inhibition in early life leads to renal abnormalities, including poorly developed renal medulla, papillary atrophy, hydronephrosis, inability to concentrate the urine, polyuria, polydipsia, renal failure, and anemia. At the core of such complex phenotype is the presence of unique vascular abnormalities: the renal arterioles do not branch or elongate properly and they have disorganized, concentric hypertrophy. This lesion has been puzzling because it is often found in hypertensive individuals whereas mutant or pharmacologically inhibited animals are hypotensive. Remarkably, when renin cells are ablated with diphtheria toxin, the vascular hypertrophy does not occur, suggesting that renin cells per se may contribute to the vascular disease. To test this hypothesis, on a Ren1(c-/-) background, we generated mutant mice with reporter expression (Ren1(c-/-); Ren1(c)-Cre; R26R. mTmG and Ren1(c-/-); Ren1(c)-Cre; R26R. LacZ) to trace the fate of renin(null) cells. To assess whether renin(null) cells maintain their renin promoter active, we used Ren1(c-/-); Ren1(c)-YFP mice that transcribe YFP (yellow fluorescent protein) directed by the renin promoter. We also followed the expression of Akr1b7 and miR-330-5p, markers of cells programmed for the renin phenotype. Contrary to what we expected, renin(null) cells did not die or disappear. Instead, they survived, increased in number along the renal arterial tree, and maintained an active molecular memory of the myoepitheliod renin phenotype. Furthermore, null cells of the renin lineage occupied the walls of the arteries and arterioles in a chaotic, directionless pattern directly contributing to the concentric arterial hypertrophy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available