Deposition of platelet-derived microparticles in podocytes contributes to diabetic nephropathy
Deposition of platelet-derived microparticles in podocytes contributes to diabetic nephropathy
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DOI：
10.1007/s11255-022-03332-z
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发表时间：
2022-08
影响因子：
2
通讯作者：
Si-jia Huang;Yang Zhang;G. Wang;Jian Lu;Pei-pei Chen;Jia Xiu Zhang;X. Li;B. Yuan;X. Liu;Tao Jiang;Meng Ying Wang;W. T. Liu;X. Ruan;B. C. Liu;K. Ma
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文献类型：
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作者：
Si-jia Huang;Yang Zhang;G. Wang;Jian Lu;Pei-pei Chen;Jia Xiu Zhang;X. Li;B. Yuan;X. Liu;Tao Jiang;Meng Ying Wang;W. T. Liu;X. Ruan;B. C. Liu;K. Ma
背景糖尿病肾病（DN）是发达国家终末期肾病的主要原因。足细胞损伤是参与DN进展的关键细胞事件。我们以前的研究表明，血小板衍生微粒（PMPs）介导的内皮损伤在糖尿病大鼠。本研究旨在探讨是否PMPs沉积在足细胞，并评估其对足细胞损伤的DN. MethodsPMPs在足细胞的沉积进行了评估，免疫荧光染色和电子显微镜。采用过碘酸-希夫染色法观察肾组织病理学变化，电镜观察肾组织超微结构变化。免疫组化染色和westernblot检测炎性细胞因子和细胞外基质蛋白的表达。结果PMPs广泛沉积于糖尿病患者和动物模型肾小球足细胞中，与DN进展密切相关。有趣的是，阿司匹林治疗显着抑制PMPs在糖尿病大鼠肾小球的积累，减轻系膜基质扩张和足突融合，并减少炎症细胞因子的蛋白表达和细胞外基质分泌。体外研究进一步证实了PMPs在足细胞中的沉积。此外，PMP刺激可通过降低足细胞podocin蛋白表达，增加α-SMA和FN蛋白表达，诱导足细胞发生表型转变，并与炎性细胞因子的产生有关。
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease in the developed world. Podocyte injury is a critical cellular event involved in the progression of DN. Our previous studies demonstrated that platelet-derived microparticles (PMPs) mediated endothelial injury in diabetic rats. This study aimed to investigate whether PMPs are deposited in podocytes and to assess their potential effects on podocyte injury in DN.MethodsThe deposition of PMPs in podocytes was assessed by immunofluorescent staining and electron microscopy. The changes in renal pathology and ultra-microstructure were assessed by periodic acid-Schiff staining and electron microscopy, respectively. The expression of inflammatory cytokines and extracellular matrix proteins was measured by immuno-histochemical staining and western blot.ResultsPMPs were widely deposited in podocytes of glomeruli in diabetic patients and animal models and closely associated with DN progression. Interestingly, aspirin treatment significantly inhibited the accumulation of PMPs in the glomeruli of diabetic rats, alleviated mesangial matrix expansion and fusion of foot processes, and decreased the protein expression of inflammatory cytokines and extracellular matrix secretion. An in vitro study further confirmed the deposition of PMPs in podocytes. Moreover, PMP stimulation induced the phenotypic transition of podocytes through decreased podocin protein expression and increased protein expression of α-SMA and fibronectin, which was correlated with increased production of inflammatory cytokines.ConclusionOur findings demonstrated for the first time that the deposition of PMPs in podocytes contributed to the development of DN.