Curcumin alleviates renal fibrosis in chronic kidney disease by targeting the circ_0008925-related pathway

Background: Curcumin has been shown to inhibit renal fibrosis, but whether curcumin mediates renal fibrosis progression by regulating the circular RNA (circRNA)-related pathway remain unclear. Methods: TGF-β1 was used to construct renal injury and fibrosis cell model. Cell growth was evaluated by cell counting kit 8 assay, EdU assay and flow cytometry. Fibrosis marker and interleukin 6 signal transducer (IL6ST) protein levels were measured using western bolt analysis. Inflammation factor concentrations were determined by ELISA. Circ_0008925, miR-204-5p and IL6ST expression was assessed by qRT-PCR. Unilateral ureteral obstruction (UUO) mice models were constructed to assess the role of curcumin in vivo. Results: Curcumin treatment alleviated TGF-β1-induced HK-2 cell apoptosis, inflammation and fibrosis in vitro, as well as relieved renal injury in UUO mice models in vivo. Circ_0008925 was highly expressed in TGF-β1-induced HK-2 cells and its expression was inhibited by curcumin. Circ_0008925 could sponge miR-204-5p to positively regulate IL6ST. The inhibition effect of curcumin on TGF-β1-induced HK-2 cell injury and fibrosis was reversed by circ_0008925 overexpression, miR-204-5p inhibitor or IL6ST upregulation. Besides, circ_0008925 knockdown inhibited TGF-β1-induced HK-2 cell injury and fibrosis by suppressing IL6ST expression. Conclusion: Curcumin relieved renal fibrosis through regulating circ_0008925/miR-204-5p/IL6ST axis.