CTGF mediates high-glucose induced epithelial-mesenchymal transition through activation of -catenin in podocytes

摘要

Objective: It is known that connective tissue growth factor (CTGF) and -catenin are involved in DN; however, the underlying molecular mechanisms remain unknown. Here we hypothesized that podocytes undergo epithelial-mesenchymal transition (EMT) in high-glucose condition and CTGF mediates high-glucose induced EMT by activating -catenin in podocytes.Methods: The differentiated podocytes were cultured and divided into three groups: the normal glucose group (5mmol/L glucose), the high-glucose group (30mmol/L glucose), and the osmotic control group (5mmol/L glucose supplemented with 25mmol/L mannitol). The morphology of cultured podocytes was observed under phase contrast microscopy. To study the relevant markers of EMT, as well as CTGF and -catenin, the mRNA and protein expressions were analyzed by real-time PCR and western blotting, respectively. In addition, the effects of inhibition CTGF by anti-CTGF antibody on high-glucose-induced EMT and -catenin expression in podocytes were studied.Results: High glucose not only induced phenotypic transition of podocytes but also increased the expression of CTGF and -catenin. Under high-glucose condition, podocytes underwent EMT, which were demonstrated by downregulation of nephrin and upregulation of desmin. Moreover, high-glucose-induced EMT and -catenin overexpression in podocytes were attenuated by anti-CTGF antibody.Conclusion: CTGF and -catenin are involved in the EMT of podocytes in diabetes. CTGF mediates high-glucose induced EMT through activation of -catenin in podocytes. CTGF inhibition may protect podocytes from EMT in diabetes.