Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGFβ.

ABSTRACT: Despite the wide use of angiotensin II receptor blockers in the treatment of Alport syndrome (AS), the mechanism as to how angiotensin II receptor blockers prevent interstitial fibrosis remains unclear. Here, we report that treatment of olmesartan effectively targets the feedback loop between the renin-angiotensin system (RAS) and transforming growth factor β (TGFβ) signals in tubular epithelial cells and preserves renal angiotensin-converting enzyme 2 (ACE2) expression in the kidney of Col4a3-/- mice, a murine model of experimental AS. Morphology analyses revealed amelioration of kidney fibrosis in Col4a3-/- mice by olmesartan treatment. Upregulation of TGFβ and activation of its downstream in Col4a3-/- mice were attenuated by olmesartan in Col4a3-/- mice. Intriguingly, TGFβ expression wa

SUBMITTER: Suh SH 

PROVIDER: S-EPMC6695622 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature