Induction of monocyte chemoattractant protein-1 expression in human mesangial cells by angiotensin II: role of c-Jun N-terminal kinase-c-Jun/activator protein-1 signal pathway.
- Author:
Ai-Hua ZHANG
1
;
Song-Ming HUANG
;
Gui-Xia DING
;
Yuan-Jun WU
;
Wei-Zhen ZHANG
;
Hong-Mei WU
;
Li FEI
;
Mei GUO
;
Rong-Hua CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Angiotensin II; pharmacology; Animals; Cells, Cultured; Chemokine CCL2; metabolism; Glomerular Mesangium; cytology; metabolism; Glomerulonephritis; metabolism; Humans; JNK Mitogen-Activated Protein Kinases; metabolism; Male; Proto-Oncogene Proteins c-fos; metabolism; Proto-Oncogene Proteins c-jun; metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; drug effects; Transcription Factor AP-1; metabolism
- From: Chinese Journal of Pathology 2004;33(6):550-554
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of c-Jun N-terminal kinase (JNK)-c-Jun/activator protein-1 (AP-1) signal pathway in expression of monocyte chemoattractant protein-1 (MCP-1) in experimental rat glomerulonephritis.
METHODSNephrotoxic sera nephritis (NTN) was induced by injection of anti-GBM antibody into the tail veins of rats. Electrophoretic mobility shift assay (EMSA) and non-radioactive kinase assay were used to detect the activity of AP-1 and JNK in kidneys and angiotensin II-stimulated human mesangial cells. Ribonuclear protection assay was used to detect MCP-1 expression in cultured human mesangial cells.
RESULTSSignificant up-regulation of JNK and AP-1 was observed in NTN rats (3.82 +/- 0.58) folds and (5.36 +/- 0.61) folds, as compared with the controls. Supershift assay demonstrated that c-Jun and c-Fos were the predominant subunits involved. Activation of JNK and AP-1 significantly correlated with MCP-1 expression in NTN rats. Angiotensin II enhanced the expression of MCP-1 and activation of JNK and AP-1 in cultured human mesangial cells in a dose-dependent manner, with maximal stimulation seen at 100 nmol/L (20.99 +/- 4.71) folds, (6.91 +/- 1.65) folds and (7.82 +/- 1.32) folds respectively. Significant down-regulation of AP-1 activation and MCP-1 expression were observed in angiotensin II-induced human mesangial cells pretreated with JNK specific inhibitor SP600125.
CONCLUSIONSAngiotensin II and MCP-1 may play an important role in glomerulosclerosis via the JNK-c-Jun/AP-1 signal pathway.
