Objective    To examine the effect of AP-1 on high glucose induced epithelial-mesenchymal-transition in cultured human kidney proximal tubular epithelial cell (HK2).      Methods    The cultured HK2 cells were divided into three groups: normal glucose group (NG)

high glucose group (HG)

activator protein-1 (AP-1) inhibited group (AG). The morphological changes of HK2 cells were observed by inverted microscope and electron microscope. The proteins of α-smooth muscle actin (α-SMA) and cytokeratin (CK) were determined by immunocytochemistry. The activity of activator protein-1 (AP-1) was assessed with electrophoretic mobility shift assay (EMSA). RT-PCR was used to detect the mRNA expression of CK. Western blot was used to detect the protein expression of α-SMA.     Results    The HK2 cells stimulated with high glucose became elongated and the number of microvilli decreased

but the number of rough endoplasmic reticulum increased. The level of AP-1 binding activity was increased by 79.22% after high glucose treatment

compared with that of normal glucose group

but decreased by 51.19% after the treatment of AP-1 inhibitor

compared with that in high glucose group. Cultured with high glucose

the expressions of CK mRNA and protein significantly decreased (P0.05)

but they significantly increased in AP-1 inhibited group (P0.05). Upon the stimulation of high glucose

the expression of α-SMA protein increased markedly (P0.05)

while it significantly decreased in AP-1 inhibited group (P0.05).      Conclusion    High glucose induces transdifferentiation of renal tubular cells probably through the activation of AP-1.