Aspirin mediates protection from diabetic kidney disease by inducing ferroptosis inhibition

• DOI: 10.1371/journal.pone.0279010
• Publication Date: 2022-12-14T18:34:35Z
• Authors: Ziyu Wu; Dan Li; Dingyuan Tian; Xuejun Liu; Zhongming Wu
• Keywords: GPX4; Pathogenesis

Diabetic kidney disease (DKD) progression can be predicted by abnormalities in the tubulointerstitial lining, and their treatment may useful for preventing disease. DKD is a progressive that contributes to renal tubular cell death, but its underlying mechanisms remain unclear. Ferroptosis novel term linked lipid hydroperoxidation, it plays an important role pathogenesis of DKD. Overexpression cyclooxygenase-2 (COX2), enzyme proximal tubule, causes cellular redox damage It remains unknown whether COX2 exacerbates accelerating ferroptosis kidneys diabetic mice. HK-2 cells cultured high glucose exhibited ferroptosis, which was inhibited inhibitors. Additionally, alterations sensors metabolism, such as glutathione peroxidase 4 (GPX4) activity, reduced (GSH) levels changes mitochondrial morphology, were observed glucose-cultured cells. mice manifested injury deranged physiological indices, mitigated ferrostatin-1 (Fer-1). Importantly, these perturbations ameliorated downregulating COX2. In addition, increased elevated daibetic kindney. To explore relevance knocked down from decreased sensitivity under conditions. RSL-3-treated cells, improved with aspirin, confirmed Furthermore, also suppressed decreasing treated retarded progression. conclusion, our results demonstrated development diabetes-related through downregulation thus retarding Our findings support renoprotective mechanism aspirin inhibits activation, identify potential target establish integral process regulated expression profiles.