Characterization of the intrarenal renin-angiotensin system in experimental alport syndrome

The American Journal of Pathology
Eun Hui BaeJames W Scholey

Abstract

Blockade of the renin-angiotensin system attenuates the progression of experimental and clinical Alport syndrome (AS); however, the underlying mechanism(s) remains largely unknown. We evaluated the renin-angiotensin system in 4- and 7-week-old homozygous for collagen, type IV, α3 gene (Col4A3(-/-)) and wild-type mice, a model of AS characterized by proteinuria and progressive renal injury. Renal angiotensin (Ang) II levels increased, whereas renal Ang-(1-7) levels decreased in 7-week-old Col4a3(-/-) mice compared with age-matched controls; these changes were partially reversed by recombinant angiotensin-converting enzyme 2 (ACE2) treatment. The expression of both the angiotensinogen and renin protein increased in Col4a3(-/-) compared with wild-type mice. Consistent with the Ang-(1-7) levels, the expression and activity of kidney ACE2 decreased in 7-week-old Col4a3(-/-) mice. The urinary excretion rate of ACE2 paralleled the decline in tissue expression. Expression of an Ang II-induced gene, heme oxygenase-1, was up-regulated in the kidneys of 7-week-old Col4a3(-/-) mice compared with wild-type mice by microarray analysis. Heme oxygenase-1 (HO-1) protein expression was increased in kidneys of Col4a3(-/-) mice and normalized by t...Continue Reading

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Citations

Aug 31, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Dominic Cosgrove, Shiguang Liu
Sep 21, 2017·Current Hypertension Reports·Silas CulverHelmy M Siragy
Oct 19, 2017·Current Opinion in Nephrology and Hypertension·Vanessa R Williams, James W Scholey
Dec 12, 2017·Canadian Journal of Kidney Health and Disease·Amber O MolnarKara Schick-Makaroff
Feb 26, 2019·Transplantation·Zahraa Mohammed-AliAna Konvalinka
May 30, 2019·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Satoshi KidoguchiTakashi Yokoo
Mar 8, 2020·Scientific Reports·Hong Sang ChoiEun Hui Bae
Nov 17, 2020·Frontiers in Molecular Biosciences·Federica SaponaroRiccardo Zucchi
Feb 23, 2021·The Korean Journal of Internal Medicine·Sang Heon SuhEun Hui Bae

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