Sulforaphane alleviates renal fibrosis through dual regulation on mTOR-mediated autophagy pathway.

Renal fibrosis is a common pathological process of progressive chronic kidney disease (CKD). However, effective therapy is constrained currently. Autophagy is an important mechanism in kidney injury and repairment but its exact role in renal fibrosis was discrepant according to previous studies. Sulforaphane (SFN), a natural plant compound, has been explored as a promising nutritional therapy for a variety of diseases. But the salutary effect and underlying mechanism of SFN on CKD have not been fully elucidated. In this study, we investigated the effect of SFN on renal fibrosis in unilateral ureteral obstruction (UUO) mice. Then we examined the regulatory effect of SFN on autophagy-related proteins in renal fibroblasts and renal tubular epithelial cells. Our results showed that sulforaphane could significantly alleviate renal fibrosis in UUO mice. In vitro, the expression levels of autophagy-related protein showed that SFN could upregulate the autophagy activity of renal interstitial fibroblasts and downregulate the autophagy activity of renal tubular epithelial cells. Furthermore, we found that phosphorylated mTOR protein levels was reduced in renal fibroblasts and increased in renal tubular epithelial cells after SFN treatment. Our results strongly suggested that SFN could alleviate renal fibrosis through dual regulation of mTOR-mediated autophagy pathway. This finding may provide a new perspective on the renal salutary effect of SFN and provide a preclinical rationale for exploring the therapeutic potential of SFN to slow down renal fibrosis.