Adiponectin Reduces Glomerular Endothelial Glycocalyx Disruption and Restores Glomerular Barrier Function in a Mouse Model of Type 2 Diabetes

Author:

Fawaz Sarah1,Martin Alonso Aldara1,Qiu Yan1ORCID,Ramnath Raina1,Stowell-Connolly Holly1,Gamez Monica1ORCID,May Carl1,Down Colin1,Coward Richard J.1,Butler Matthew J.1,Welsh Gavin I.1,Satchell Simon C.1,Foster Rebecca R.1ORCID

Affiliation:

1. Bristol Renal, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, U.K.

Abstract

Adiponectin has vascular anti-inflammatory and protective effects. Although adiponectin protects against the development of albuminuria, historically, the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnCs). In diabetes, eGlx dysfunction occurs before podocyte damage; hence, we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD). Globular adiponectin (gAd) activated AMPK signaling in human GEnCs through AdipoR1. It significantly reduced eGlx shedding and the tumor necrosis factor-α (TNF-α)–mediated increase in syndecan-4 (SDC4) and MMP2 mRNA expression in GEnCs in vitro. It protected against increased TNF-α mRNA expression in glomeruli isolated from db/db mice and against expression of genes associated with glycocalyx shedding (namely, SDC4, MMP2, and MMP9). In addition, gAd protected against increased glomerular albumin permeability (Ps’alb) in glomeruli isolated from db/db mice when administered intraperitoneally and when applied directly to glomeruli (ex vivo). Ps’alb was inversely correlated with eGlx depth in vivo. In summary, adiponectin restored eGlx depth, which was correlated with improved glomerular barrier function, in diabetes. Article Highlights

Funder

British Heart Foundation

Diabetes UK

David Telling Charitable Trust

Wellcome Trust Partnership Award Fellowship

MRC confidence in concepts

Biomarker Enterprise to Attack Diabetic Kidney Disease (BEAt-DKD) consortium

Kidney Research UK

Publisher

American Diabetes Association

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Molecular mechanism of renal lipid accumulation in diabetic kidney disease;Journal of Cellular and Molecular Medicine;2024-06

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