[Advanced glycation end products induce expression of PAI-1 in cultured human proximal tubular epithelial cells through NADPH oxidase dependent pathway].

ABSTRACT

AIM: To investigate the effects of advanced glycation end products (AGES) on secretion of plasminogen activator inhibitor-1(PAI-1)by human proximal tubular epithelial cells and its NADPH oxidase dependent pathway. METHODS: Human proximal tubular epithelial cells were cultured in vitro with indicated concentration of AGES modified human serum albumin (AGES-HSA). NADPH oxidase activity were detected by lucigenin-enhanced chemiluminescence. The production of PAI-1 was evaluated by enzyme-linked immunoadsorbent assay (ELISA). The PAI-1 mRNA expression was assayed by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: AGES-HSA were associated with enhanced oxidative stress and NADPH oxidase activity. AGES-HSA upregulated the expression of PAI-1 mRNA and protein with dose and time dependent fashion. AGES-HSA-induced PAI-1 expression were significantly suppressed by the NAD(P)H oxidase inhibitors DPI, apocynin or O2- scavenger SOD. CONCLUSION: AGES-HSA stimulate tubular epithelial cells to produce PAI-1 through activation of NADPH oxidase.