[Mechanism of Mudan Granules in protecting podocytes and improving diabetic nephropathy by regulating PPARγ/FABP4...

This study investigated the therapeutic effect of Mudan Granules on diabetic nephropathy(DKD) and preliminarily elucidated its potential mechanism using transcriptomics. A DKD rat model was established by streptozotocin(STZ) induction. Sixty rats were randomly divided into a control group, a model group, low-, medium-, and high-dose Mudan Granules groups, and an positive control(enalapril) group. Drug efficacy was evaluated by measuring blood glucose, renal function, and the urine albumin-to-creatinine ratio. Renal pathological and ultrastructural changes were observed using HE, PAS, and Masson staining, as well as transmission electron microscopy. Furthermore, RNA sequencing was employed to identify differentially expressed genes in renal tissue, followed by pathway enrichment analysis. Key pathways and proteins were validated using immunohistochemistry and Western blot. The results showed that Mudan Granules significantly reduced urinary protein levels in DKD rats and alleviated pathological injuries such as glomerular mesangial hyperplasia, basement membrane thickening, and podocyte foot process fusion. Transcriptomic analysis revealed significant enrichment of the peroxisome proliferator-activated receptor(PPAR) signaling pathway. Mechanistic validation demonstrated that Mudan Granules up-regulated the expression of peroxisome proliferator-activated receptor γ(PPARγ) and the podocyte marker protein Nephrin in renal tissues, while down-regulating the expression of its downstream target fatty acid binding protein 4(FABP4) and the fibrosis marker protein α-smooth muscle actin(α-SMA). In conclusion, Mudan Granules exert a clear renoprotective effect in STZ-induced DKD rats. Its mechanism may be related to the activation of the PPARγ signaling pathway, the regulation of the PPARγ/FABP4 axis, and subsequent inhibition of podocyte epithelial-mesenchymal transition(EMT), thereby protecting podocyte structural integrity.