Deposition of platelet-derived microparticles in podocytes contributes to diabetic nephropathy

• Published in: International urology and nephrology 2023-02, Vol.55 (2), p.355-366
• Main Authors: Huang, Si Jia, Zhang, Yang, Wang, Gui Hua, Lu, Jian, Chen, Pei Pei, Zhang, Jia Xiu, Li, Xue Qi, Yuan, Ben Yin, Liu, Xiao Qi, Jiang, Ting Ting, Wang, Meng Ying, Liu, Wen Tao, Ruan, Xiong Zhong, Liu, Bi Cheng, Ma, Kun Ling
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Aspirin; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - pathology; Cytokines; Cytokines - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetic Nephropathies - complications; Diabetic nephropathy; Electron microscopy; End-stage renal disease; Extracellular matrix; Fibronectin; Inflammation; Kidney diseases; Medicine; Medicine & Public Health; Microparticles; Microscopy; Nephrology; Nephrology - Original Paper; Nephropathy; Platelets; Podocytes - metabolism; Protein expression; Proteins; Rats; Urology
• ISSN: 1573-2584; 0301-1623; 1573-2584
• DOI: 10.1007/s11255-022-03332-z

Background Diabetic 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. Methods The 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. Results PMPs 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. Conclusion Our findings demonstrated for the first time that the deposition of PMPs in podocytes contributed to the development of DN.