Aspirin attenuates podocyte injury in diabetic rats through overriding cyclooxygenase-2-mediated dysregulation of LDL receptor pathway
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This study aimed to investigate the effects of aspirin on podocyte injury and its underlying mechanisms in diabetic nephropathy (DN).
Eight-week-old male Sprague–Dawley rats were divided into three groups: non-diabetic rats (Control), streptozotocin-induced diabetic rats (DM), and diabetic rats treated with aspirin (DM + Aspirin) for 12 weeks. Intracellular lipid accumulation was evaluated by Oil Red O staining and quantitative free cholesterol assays. Podocyte injury and the levels of COX-2, inflammatory cytokines, and low-density lipoprotein receptor (LDLr) pathway-related proteins were evaluated by electron microscopy, immunohistochemical staining, and Western blotting, respectively.
Lipid levels and urinary albumin–creatinine ratios were higher in the DM rats than in the Control rats. Periodic acid-Schiff staining showed glomerular hypertrophy and mild mesangial area widening in the DM rats. Electron microscopy showed that the podocyte foot processes were significantly flattened or absent in the DM rats. The protein expression levels of WT-1 and nephrin in the podocytes of DM rats were reduced. Interestingly, lipid accumulation in the kidneys of DM rats was significantly increased due to increased protein expression levels of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), SREBP-2, cyclooxygenase-2 (COX-2), and inflammatory cytokines. Confocal immunofluorescent staining showed that COX-2 and WT-1 were co-expressed. Furthermore, COX-2 protein expression levels were positively correlated with LDLr protein expression levels. However, when COX-2 expression was inhibited by aspirin, these changes in the DM rats were significantly attenuated.
Aspirin attenuates podocyte injury in DN, which may be through COX-2-mediated dysregulation of LDLr pathway.
KeywordsAspirin Cyclooxygenase-2 LDL receptor Podocyte injury Diabetic nephropathy
This work was supported by the National Natural Science Foundation of China (Grant 81470957), the Jiangsu Province Social Development Project (BE2018744), the Project for Jiangsu Provincial Medical Talent (ZDRCA2016077), the Jiangsu Province Six Talent Peaks Project (2015-WSN-002), the Fundamental Research Funds for the Central Universities (KYCX18-0182, KYCX17-0169, KYZZ15-0061), the Jiangsu Province Ordinary University Graduate Research Innovation Project (SJZZ16-004), and the Project of Nanjing Municipal Committee for Health and Family Planning (YKK17280).
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Conflict of interest
The authors declare that they have no conflict of interest.
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