Objective: It is known that connective tissue growth factor (CTGF) and β-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 β-catenin in podocytes.
Methods: The differentiated podocytes were cultured and divided into three groups: the normal glucose group (5 mmol/L glucose), the high-glucose group (30 mmol/L glucose), and the osmotic control group (5 mmol/L glucose supplemented with 25 mmol/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 β-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 β-catenin expression in podocytes were studied.
Results: High glucose not only induced phenotypic transition of podocytes but also increased the expression of CTGF and β-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 β-catenin overexpression in podocytes were attenuated by anti-CTGF antibody.
Conclusion: CTGF and β-catenin are involved in the EMT of podocytes in diabetes. CTGF mediates high-glucose induced EMT through activation of β-catenin in podocytes. CTGF inhibition may protect podocytes from EMT in diabetes.
Keywords: CTGF; diabetes; epithelial–mesenchymal transition; podocyte; β-Catenin.