Catalpol attenuates EMT by inhibiting Wnt/β-catenin and TGF-β/Smads signaling to alleviate kidney fibrosis

Abstract

Purpose: To determine the anti-fibrosis effect and underlying mechanism of action of catalpol (CAT) in chronic kidney disease (CKD). Methods: Forty (40) rats were randomly divided into a sham group (10 rats) and a unilateral ureteral obstruction (UUO) model group (30  rats) which was further randomly subdivided into three groups of ten (10) rats each: the UUO model group, UUO + CAT low-dose group,  and UUO + CAT high-dose group. HK-2 cells were stimulated with TGF-β1 for in vitro studies. Renal injury and fibrotic lesions were determined by H&E and Masson’s staining. Key proteins of TGF-β/Smads and Wnt/β-catenin signaling pathways involved in epithelial- mesenchymal transition (EMT) were determined by immunohistochemistry, immunofluorescence staining and Western blotting. Results: Catalpol downregulated the expression of α-SMA (p < 0.05) and upregulated the expression of E-cadherin (p < 0.05) stimulated  by TGF-β1 and LiCl in HK-2 cells, which is consistent with the role of DKK1 in vitro. CAT ameliorated renal fibrosis and repressed the  expression of key proteins of TGFβ/Smads and Wnt/β-catenin pathways in UUO rats. Conclusion: Catalpol inhibits EMT and alleviates  kidney fibrosis by suppressing the hyperactivation of TGF-β/Smad and Wnt/β-catenin signaling pathways. Therefore, CAT is a promising  therapeutic drug for renal fibrosis.