Role of Snail in the renal tubular epithelial-mesenchymal- transition mediated by activator protein-1

AIM: To study the role of Snail in the renal tubular epithelial-myofibroblast transdifferentiation and fibronectin synthesis mediated by activator protein-1. METHODS: The cultured HK2 cells were divided into three groups: normal glucose group (NG), high glucose group (HG) and activator protein-1 (AP-1) inhibited group (AG). Concentration of fibronectin into the culture media was determined by ELISA. The activity of activator protein-1 was assessed with electrophoretic mobility shift assay (EMSA). The protein of E-cadherin and vimentin was determined by immunocytochemistry. RT-PCR was used to detect the mRNA expression of vimentin and Snail. Western blotting was used to detect the protein expression of E-cadherin.RESULTS: Secreted FN level was significantly up-regulated by the stimulation of high glucose (P<0.05), but the level significantly decreased in AP-1 inhibited group than that in high glucose group (P<0.05). AP-1 binding activity was significantly stimulated by high glucose and the inhibitor of AP-1 inhibited high glucose induced AP-1 activation in HK-2. High glucose induced Snail mRNA expression, while the level significantly decreased in AP-1 inhibited group than that in high glucose group (P<0.05). Upon the stimulation with high glucose, the expression of E-cadherin protein decreased markedly (P<0.05), while the level was higher in AP-1 inhibited group than that in high glucose group (P<0.05). Cultured with high glucose, the expression of vimentin mRNA and protein significantly increased (P<0.05), but the level significantly decreased in AP-1 inhibited group than that in high glucose group (P<0.05). CONCLUSION: High glucose induces the expression of Snail through the activation of AP-1. The expression of Snail downregulates E-cadherin expression and induces transdifferentiation of renal tubular cells characterized by vimentin expression and fibronectin synthesis.