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


CONCLUSIONS
AGES-HSA stimulate tubular epithelial cells to produce PAI-1 through activation of NADPH oxidase.
Fu
Bi-ling
BL
Department of Nephrology, Nanfang Hospital, Southern Medical Unversity, Guangzhou 510515, China. fblfbl1982@163.com
Guo
Zhi-jian
ZJ
Tian
Jian-wei
JW
Liu
Zhi-qiang
ZQ
Cao
Wei
W
D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D015398:Signal Transduction
D017127:Glycation End Products, Advanced; D017395:Plasminogen Activator Inhibitor 1; D012709:Serum Albumin; D019255:NADPH Oxidases