Abstract: Objective To investigate the effect of EGFR signaling pathway in apoptosis of human renal proximal tubular epithelial cells (HK-2) under high concentration of glucose. Methods HK-2 cells were cultured in vitro and divided into 4 groups: normal glucose group, mannitol control group, high glucose group, high glucose plus EGFR inhibitor group. Western blot analysis was used to determine the expression of phosphorylated EGFR, total EGFR, cleaved caspase-3、BAX, BCL-2 and β-actin. MTT assay was used to detect the proliferation of cells. Apoptosis of HK-2 was also analyzed by flow cytometry. Results Compared with normal glucose group and mannitol control group, the number of cell apoptosis (cleaved caspase-3 expression and BAX/BCL-2 ratio), activity of EGFR and endoplasmic reticulum stress (ERS) are significantly increased in HK-2 cells in high glucose group (P＜0. 01). Specific EGFR inhibition (AG1478) inhibited high glucose-induced HK-2 cell apoptosis（P＜0.05）, EGFR activation（P＜0.05）, endoplasmic reticulum stress（P＜0.05）. Conclusions Inhibition of EGFR activation may prevent high glucose-induced HK-2 cell apoptosis through decreasing endoplasmic reticulum stress.

Key words: diabetic nephropathy, HK-2 cell, EGFR, apoptosis, endoplasmic reticulum stress