The Role of the ERK Signaling Pathway on High Glucose-Induced Epithelial-Mesenchymal Transition in Cultured Human Renal Tubular Epithelial Cells

摘要

Aim: To observe the role of ERK signaling pathway on high glucose induced epithelial-mesenchymal transition, and to investigate the mechanism of tubulointerstitial fibrosis associated with diabetic nephropathy. Methods: The human proximal tubular epithelial cell line (HK-2) were respectively treated with normal glucose, high glucose, and high glucose with specific ERK inhibitor PD98059 or D-mannitol for 72 h. The protein expression level of alpha-SMA and CK18 was assessed by immuno-cytochemistry The ERK and p-ERK expression level was determined by Western blotting. Results: (1) In control group, we found that CK18 was highly expressed in the cytoplasm of tubular epithelial cells, but no alpha-SMA was observed. However, high glucose increased the expression of alpha-SMA and reduced the CK18 expression Interestingly, combining treatment with high glucose and PD98059, the expression level of CK18 and alpha-SMA was reversed. D-mannitol can also reverse this results. (2) In control group, the expression level of total ERK1/2 or phospho-ERK1/2 were rarely, While high glucose significantly promote the expression of phospho-ERK1/2 (P 0.05). In addition, phospho-ERK1/2 was decreased a lot following treatment with ERK inhibitor PD98059 (P 0.05), while total ERK1/2 had no differences with control group. No significant differences between control group and D-mannitol group was observed. Conclusion: This study suggests that ERK may play an important role in the high glucose-induced EMT in tubular epithelial cells, and EMT was partly inhibited through suppressing the progress of tubulointerstitial fibrosis according to the inhibition of ERK.