Role of NT-κB in monocytes-induced HK-2 cells transdifferentiation / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effects of monocytes on phenotypic changes of human proximal tubular HK-2 cells and the mechanism.Methods Monocytes were co-cultured with HK-2 cells.Morphological changes of HK-2 cells were detected by inverted phase contrast microscope.Expressions of E-cadherin,α-SMA and fibronectin were assessed by RT-PCR,Western blotting and immunocytochemical staining.Flow cytometry techniques was applied to evaluate intercellular cell adhesion molecule-1 (ICAM-1) expression on HK-2 cells.The intracellular signal was investigated by gene microarr ay.Results The typical epithelial cell morphology of HK-2 cells disappeared after co-culture with monocytes,accompanied by decreased E-cadherin expression and increased α-SMA and fibronectin expression (all P＜0.05).The expression of ICAM-1 on HK-2 cells was increased by monocytes stimulation.Interestingly,administration of CD18 antibody directly inhibited the phenotypic change of HK-2 cells.Furthermore,NF-κB signaling might be critical in mediating this process,and blockade of this signaling pathway could inhibit 1CAM-1 expression and epithelial mesenchymal transition (EMT) formation.Conclusion Monocytes can directly induce EMT of HK-2 cells via up-regulating ICAM-1 through NF-κB signaling pathway.