Role of miR34a-KLF4 signaling pathway in podocyte injury in obesity

Abstract Objective This study aims to investigate the involvement of the miR-34a/KLF4 signaling pathway in obesity-related kidney injury using a mouse model induced by a High-Fat Diet and podocyte injury induced by Palmitic Acid. Methods An obese mouse model was induced through high-fat feeding, followed by analysis of renal pathology and immunohistochemistry, as well as detection of miR-34a RNA and Kruppel-like factor 4(KLF4) levels. In vitro experiments involved treating podocytes with varying concentrations of Palmitic Acid, conducting Oil Red O staining, assessing related indicators and apoptosis, and transfecting miR-34a mimics or inhibitors to evaluate their effects. A luciferase assay was performed to validate the targeting relationship. Results The High-Fat Diet successfully established the obese mouse model, leading to a significant increase in glomerular volume. Renal tissue exhibited decreased levels of KLF4 and Nephrin, alongside increased levels of Bak and Cleaved CASP9. miR-34a showed a negative correlation with KLF4 and a positive correlation with Bak, suggesting a potential induction of apoptosis through KLF4. Cell experiments demonstrated that Palmitic Acid upregulated miR-34a, downregulated KLF4, and induced podocyte apoptosis. Furthermore, miR-34a mimics exacerbated apoptosis, while miR-34a inhibitors alleviated it. The dual-luciferase assay confirmed that miR-34a targeted and inhibited KLF4. Conclusion Elevated miR-34a levels contribute to podocyte injury by inhibiting KLF4, thereby promoting the progression of obesity-related glomerulopathy.