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 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.

中文翻译：

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脂联素减少 2 型糖尿病小鼠模型中肾小球内皮糖萼的破坏并恢复肾小球屏障功能

脂联素具有血管抗炎和保护作用。尽管脂联素可以防止蛋白尿的发生，但历史上，焦点一直集中在肾小球滤过屏障（GFB）内的足细胞保护上。 GFB 中白蛋白的第一个屏障是内皮糖萼 (eGlx)，这是一种覆盖肾小球内皮细胞 (GEnC) 的表面凝胶状屏障。在糖尿病中，eGlx 功能障碍发生在足细胞损伤之前；因此，我们假设脂联素可以防止 eGlx 损伤，从而预防糖尿病肾病 (DKD) 的早期血管损伤。球状脂联素 (gAd) 通过 AdipoR1 激活人类 GEnC 中的 AMPK 信号传导。它在体外显着减少了 GEnC 中 eGlx 脱落以及 TNF-α 介导的 syndecan-4 (SDC4) 和 MMP2 mRNA 表达增加。它可以防止 db/db 小鼠分离的肾小球中 TNF-α mRNA 表达增加，并防止与糖萼脱落相关的基因（即 SDC4、MMP2 和 MMP9）的表达。此外，当腹膜内给药和直接应用于肾小球（离体）时，gAd 可防止从 db/db 小鼠分离的肾小球中肾小球白蛋白通透性（Ps'alb）增加。 Ps'alb 与体内 eGlx 深度呈负相关。总之，脂联素恢复了糖尿病患者的 eGlx 深度，这与肾小球屏障功能的改善相关。