Shenkang VII Recipe Attenuates Unilateral Ureteral Obstruction-induced Renal Fibrosis via TGF-β/Smad, NF-κB and SHH Signaling Pathway

This study aimed to explore the protective effects of the traditional Chinese Medicine formula Shenkang VII recipe (SK-7) on renal fibrosis and the mechanisms. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) in rats. The rats were then divided into 5 groups: control group (Sham operation), UUO model group, UUO model plus low to high doses of SK-7 (0.5, 1.0, or 2.0 g/kg/day, for 14 days) groups. The animals were sacrificed on the 7th or 14th day. Kidney tissues were collected for histopathological examinations (hematoxylin and eosin and Masson's trichrome staining). Immunohistochemistry was used to detect the expression of collagen type III (Col III), fibronectin (FN), alpha-smooth muscle actin (alpha-SMA), TIMP metallopeptidase inhibitor 2 (TIMP2), matrix metallopeptidase 2 (MMP2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and monocyte chemotactic protein-1 (MCP-1). The TGF-beta 1/Smad, NF-kappa B and Sonic hedgehog signaling proteins were detected by Western blotting. Our results showed that SK-7 prevented UUO-induced renal injury and accumulation of collagen fibrils. Renal fibrosis biomarkers Col III, FN, alpha-SMA and TIMP2 were increased in the rats after UUO and decreased by SK-7, while MMP2 was upregulated after treatment. SK-7 also suppressed the levels of TNF-alpha, IL-1 beta and MCP-1 in UUO rats. In addition, SK-7 inhibited activation of the TGF-beta/Smad, NF-kappa B and sonic hedgehog signaling (SHH) pathways. Taken together, these findings suggest that SK-7 may regulate the synthesis and degradation of extracellular matrix, reduce inflammation and suppress the proliferation of fibroblasts, by blocking the TGF-beta 1/Smad, NF-kappa B and SHH signaling pathways to exert its anti-renal fibrosis effect in UUO rats.