Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism
Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism
复制标题
JAML 升高通过调节足细胞脂质代谢促进糖尿病肾病。
DOI：
10.1016/j.cmet.2020.10.019
复制
发表时间：
2020-12-01
期刊：
影响因子：
29
通讯作者：
Yi, Fan
中科院分区：
文献类型：
--
作者：
Fu, Yi;Sun, Yu;Yi, Fan
足细胞中的脂质积聚是糖尿病肾病（DKD）的主要决定因素，通过介导足细胞脂质代谢来鉴定潜在的治疗靶点具有临床重要性。本研究旨在阐明JAML（junctional adhesion molecule like protein）在DKD发病机制中的作用。我们首先证实了JAML在足细胞中的表达，并发现在两种不同的糖尿病小鼠模型中，足细胞特异性缺失JAML改善了足细胞损伤和蛋白尿。我们进一步证明了JAML通过SIRT1介导的SREBP1信号在调节足细胞脂质代谢中的新作用。在阿霉素肾病小鼠中也发现了类似的结果。重要的是，我们观察到JAML在DKD和其他类型的蛋白尿性肾病受试者的肾小球中的较高表达，并且JAML的水平与脂质积聚和肾小球滤过率相关，这表明JAML可能是蛋白尿性肾病的有吸引力的治疗靶点。
Lipid accumulation in podocytes is a major determinant of diabetic kidney disease (DKD) and identification of potential therapeutic targets by mediating podocyte lipid metabolism has clinical importance. This study was to elucidate the role of JAML (junctional adhesion molecule-like protein) in the pathogenesis of DKD. We first confirmed the expression of JAML in podocytes and found that podocyte-specific deletion of Jaml ameliorated podocyte injury and proteinuria in two different models of diabetic mice. We further demonstrated a novel role of JAML in regulating podocyte lipid metabolism through SIRT1-mediated SREBP1 signaling. Similar results were also found in mice with adriamycin-induced nephropathy. Importantly, we observed a higher expression of JAML in glomeruli from subjects with DKD and other types of proteinuric kidney diseases, and the level of JAML was correlated with lipid accumulation and glomerular filtration rate, suggesting that JAML may be an attractive therapeutic target for proteinuric kidney disease.