Conclusion
Our findings indicate that TRL can alleviate tubular epithelial-mesenchymal transition and renal fibrosis in db/db mice by upregulating Smad7 in PTCs, suggesting that TRL is a promising medicine against DKD.
Methods
The db/db mice were used as a spontaneous model of DKD and TRL solution was administered by daily gavage for 8 weeks. Indicators associated with glucose metabolism, renal function and urinary albumin were tested. Renal fibrosis in diabetic mice was evaluated by histopathological staining. Kidney transcriptomics was performed after confirming therapeutic effects of TRL on DKD mice. Molecular biology techniques and in vitro experiments were utilized for final mechanism verification.
Results
Biochemical tests revealed that TRL ameliorated renal damage and reduced microalbuminuria in DKD mice. TRL exhibited a protective effect on PTCs, effectively mitigating tubular EMT and renal fibrosis in diabetic kidneys. Transcriptomics analysis indicated that TRL may target Smad7, an inhibitor of TGF-β1 signaling, to alleviate fibrosis. Furthermore, in vitro experiments validated that silencing Smad7 abolished the therapeutic effect of TRL.