Effect of inhibitor of integrin linked kinase, QLT0267 on tubularepithelial-myofibroblast transdifferentiation of HK-2 Cells

Abstract

Objective To explore the effect and the possible pathway of different concentrations of QLT0267, which was the inhibitor of the integrin-linked kinase (ILK), on the process of high glucose-induced tubularepithelial-myofibroblast transdifferentiation (TEMT) in human renal tubular epithelial cells (HK-2). Methods HK-2 cells were exposed to 30 mmol/L GS, and TEMT model was established. After excluding the effect of high osmotic in TEMT, HK-2 cells were divided into 6 groups by different concentrations of GS and QLT0267 for 48 hours. The rate of the cell proliferation was calculated by MTT. The expression of ILK and α-smooth muscle actin (α-SMA) were determined by immunofluorescence and Western blot, and the expression of protein kinase B (AKT), phosphorylated protein kinase B (p-AKT), and E-cadherin were determined by Western blot. Results (1) The expression of ILK, p-AKT, and α-SMA in HK-2 cells were unregulated and the expression of E-cadherin was downregulated for 48 hours with glucose treating vs control (P <0.05); (2) The proliferation rate in high glucose group was higher than the group which concentration of QLT0267 was greater than 5 μmol/L (P <0.05); (3) With the concentrations of QLT0267 increased, the expression of p-AKT, α-SMA was gradually decreased (all P <0.05), and the expression of E-cadherin was gradually increased (all P <0.05). Conclusions 30 μmol/L of GS can lead to TEMT in HK-2 cell. The QLT0267 with concentration greater than 5 μmol/L may prevent the activation of ILK downstream proteins, then partially inhibits cell proliferation and TEMT in HK-2 cell. Key words: Diabetic nephropathies; Cell transdifferentiation; Protein-serine-threonine kinase