Header

UZH-Logo

Maintenance Infos

Olmesartan prevents microalbuminuria in db/db diabetic mice through inhibition of angiotensin II/p38/SIRT1-induced podocyte apoptosis


Gu, Junhui; Yang, Ming; Qi, Na; Mei, Shuqin; Chen, Jiejian; Song, Shuwei; Jing, Ying; Chen, Meihan; He, Liangliang; Sun, Lijun; Hu, Huimin; Li, Lin; Wüthrich, Rudolf P; Wu, Ming; Mei, Changlin (2016). Olmesartan prevents microalbuminuria in db/db diabetic mice through inhibition of angiotensin II/p38/SIRT1-induced podocyte apoptosis. Kidney & Blood Pressure Research, 41(6):848-864.

Abstract

BACKGROUND/AIMS: Blockage of the renin-angiotensin II system (RAS) prevents or delays albuminuria in diabetic patients. The aim of this study was to investigate the inhibitory mechanism of the angiotensin receptor blocker olmesartan on albuminuria in a murine model of diabetic nephropathy.
METHODS: Male db/db diabetic mice were fed with placebo or 20 mg/kg olmesartan by daily gavage for 12 weeks. Conditionally immortalized mouse podocytes were treated with glucose, angiotensin II, olmesartan or p38 inhibitor s8307 in different experimental conditions after differentiation.
RESULTS: Olmesartan reduced albuminuria in db/db mice without change in body weight and glycemia. The increase of apoptotic cells and decrease of podocytes in the diabetic glomerulus were prevented by olmesartan. Moreover, olmesartan restored silent mating type information regulation 1 (SIRT1) expression in diabetic glomeruli. Furthermore, olmesartan treatment suppressed p38 phosphorylation but did not restore adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation in the diabetic glomerulus. In vitro study revealed that olmesartan prevented angiotensin II/p38/SIRT1 induced podocyte apoptosis, but it only slightly prevented high glucose/AMPK/SIRT1 induced podocyte apoptosis. In addition, the p38 inhibitor s8307 reversed SIRT1 expression and angiotensin II induced podocyte apoptosis.
CONCLUSIONS: Olmesartan reduced albuminuria in diabetic nephropathy through inhibiting angiotensin II/p38/SIRT1 triggered podocyte apoptosis.

Abstract

BACKGROUND/AIMS: Blockage of the renin-angiotensin II system (RAS) prevents or delays albuminuria in diabetic patients. The aim of this study was to investigate the inhibitory mechanism of the angiotensin receptor blocker olmesartan on albuminuria in a murine model of diabetic nephropathy.
METHODS: Male db/db diabetic mice were fed with placebo or 20 mg/kg olmesartan by daily gavage for 12 weeks. Conditionally immortalized mouse podocytes were treated with glucose, angiotensin II, olmesartan or p38 inhibitor s8307 in different experimental conditions after differentiation.
RESULTS: Olmesartan reduced albuminuria in db/db mice without change in body weight and glycemia. The increase of apoptotic cells and decrease of podocytes in the diabetic glomerulus were prevented by olmesartan. Moreover, olmesartan restored silent mating type information regulation 1 (SIRT1) expression in diabetic glomeruli. Furthermore, olmesartan treatment suppressed p38 phosphorylation but did not restore adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation in the diabetic glomerulus. In vitro study revealed that olmesartan prevented angiotensin II/p38/SIRT1 induced podocyte apoptosis, but it only slightly prevented high glucose/AMPK/SIRT1 induced podocyte apoptosis. In addition, the p38 inhibitor s8307 reversed SIRT1 expression and angiotensin II induced podocyte apoptosis.
CONCLUSIONS: Olmesartan reduced albuminuria in diabetic nephropathy through inhibiting angiotensin II/p38/SIRT1 triggered podocyte apoptosis.

Statistics

Citations

Altmetrics

Downloads

16 downloads since deposited on 09 Jan 2017
16 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2016
Deposited On:09 Jan 2017 14:18
Last Modified:23 Nov 2017 08:35
Publisher:Karger
ISSN:1420-4096
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000452588
PubMed ID:27871084

Download

Download PDF  'Olmesartan prevents microalbuminuria in db/db diabetic mice through inhibition of angiotensin II/p38/SIRT1-induced podocyte apoptosis'.
Preview
Content: Published Version
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)