Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, 226000, PR China.
Department of Pharmacology, School of Medicine, Nantong University, Nantongs, 226000, PR China.
Biochem Biophys Res Commun. 2018 Nov 30;506(3):529-535. doi: 10.1016/j.bbrc.2018.09.175. Epub 2018 Oct 22.
Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus and often results in chronic renal failure. Here, we found that Interleukin 1 receptor associated kinases (IRAK1) was up-regulated in kidney in both DN patients and high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. In vivo, down regulation of IRAK1 ameliorated renal injury and function, with lower podocyte apoptosis, increased expression of Nephrin, attenuated thickness of the glomerular basement membrane and podocyte footprocess effacement. Furthermore, in vitro, down regulation of IRAK1 in podocytes treated with high glucose (HG), podocyte apoptosis and inflammatory cytokines were significantly decreased, but Nephrin increased. Meanwhile, apoptosis-related genes caspase-3/-9 were inhibited and phosphorylation levels of PI3K/Akt were dramatically down regulated. Thus, IRAK1 is one of the critical components involved in podocyte apoptosis in DN.
糖尿病肾病（DN）是糖尿病最常见的微血管并发症之一，常导致慢性肾衰竭。在这里，我们发现白细胞介素 1 受体相关激酶（IRAK1）在 DN 患者和高脂肪饮食（HFD）/链脲佐菌素（STZ）诱导的糖尿病小鼠的肾脏中均上调。在体内，IRAK1 的下调可改善肾脏损伤和功能，足细胞凋亡减少，Nephrin 表达增加，肾小球基底膜和足细胞足突融合厚度减轻。此外，在高糖（HG）处理的足细胞中下调 IRAK1，足细胞凋亡和炎性细胞因子明显减少，而 Nephrin 增加。同时，凋亡相关基因 caspase-3/-9 被抑制，PI3K/Akt 的磷酸化水平明显下调。因此，IRAK1 是 DN 中参与足细胞凋亡的关键成分之一。
