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 / 中华病理学杂志
Chinese Journal of Pathology
; (12): 550-554, 2004.
Article
en Zh
| WPRIM
| ID: wpr-283475
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WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Nephrotoxic 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.</p><p><b>RESULTS</b>Significant 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.</p><p><b>CONCLUSIONS</b>Angiotensin II and MCP-1 may play an important role in glomerulosclerosis via the JNK-c-Jun/AP-1 signal pathway.</p>
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Índice:
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Asunto principal:
Farmacología
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Angiotensina II
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Transducción de Señal
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Células Cultivadas
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Proteínas Proto-Oncogénicas c-jun
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Proteínas Proto-Oncogénicas c-fos
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Ratas Sprague-Dawley
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Factor de Transcripción AP-1
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Quimiocina CCL2
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Biología Celular
Límite:
Animals
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Humans
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Male
Idioma:
Zh
Revista:
Chinese Journal of Pathology
Año:
2004
Tipo del documento:
Article