The mechanism of sirt1 reducing albumin induced renal podocyte injury in mice

Background and purpose: This study investigates the protective effects of sirt1 on albumin-induced podocyte damage, focusing on the regulatory role of HIF-1a. Podocyte injury contributes significantly to proteinuria, a marker of chronic kidney disease (CKD) progression. Understanding the sirt1/HIF-1a pathway may provide insights into novel therapeutic strategies for CKD. Materials and methods: Cultured mouse podocytes were divided into control, albumin-induced, sirt1 agonist, and sirt1 inhibitor groups. RTqPCR was used to evaluate the expression of sirt1 and HIF-1a mRNA. Protein levels of Nephrin, podocalyxin, and TRPC6 were assessed through Western blot and immunofluorescence techniques to determine podocyte damage. Results: The albumin-induced group showed decreased Sirt1 and increased HIF-1a levels, while sirt1 agonists reversed these changes, indicating that the kidney protective effect. In contrast, sirt1 inhibitors worsened podocyte injury. Western blot and immunofluorescence confirmed a significant reduction in Nephrin and podocalyxin and an increase in TRPC6 protein expression in albumin-treated groups, which was mitigated by sirt1 activation. Conclusions: Sirt1 protects against albumin-induced podocyte damage by modulating HIF-1a, suggesting its potential as a therapeutic target for proteinuria and CKD management. This study provides a foundational understanding of sirt1's role in podocyte protection and highlights the need for further research to explore its clinical applications in preventing CKD progression.