PMID- 15634454 OWN - NLM STAT- MEDLINE DCOM- 20070320 LR - 20160818 IS - 0529-5807 (Print) IS - 0529-5807 (Linking) VI - 33 IP - 6 DP - 2004 Dec TI - [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]. PG - 550-4 AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Angiotensin II and MCP-1 may play an important role in glomerulosclerosis via the JNK-c-Jun/AP-1 signal pathway. FAU - Zhang, Ai-Hua AU - Zhang AH AD - Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, Nanjing 210008, China. FAU - Huang, Song-Ming AU - Huang SM FAU - Ding, Gui-Xia AU - Ding GX FAU - Wu, Yuan-Jun AU - Wu YJ FAU - Zhang, Wei-Zhen AU - Zhang WZ FAU - Wu, Hong-Mei AU - Wu HM FAU - Fei, Li AU - Fei L FAU - Guo, Mei AU - Guo M FAU - Chen, Rong-Hua AU - Chen RH LA - chi PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Zhonghua Bing Li Xue Za Zhi JT - Zhonghua bing li xue za zhi = Chinese journal of pathology JID - 0005331 RN - 0 (Chemokine CCL2) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Transcription Factor AP-1) RN - 11128-99-7 (Angiotensin II) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) SB - IM MH - Angiotensin II/*pharmacology MH - Animals MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Glomerular Mesangium/cytology/*metabolism MH - Glomerulonephritis/metabolism MH - Humans MH - JNK Mitogen-Activated Protein Kinases/*metabolism MH - Male MH - Proto-Oncogene Proteins c-fos/metabolism MH - Proto-Oncogene Proteins c-jun/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - Transcription Factor AP-1/*metabolism EDAT- 2005/01/07 09:00 MHDA- 2007/03/21 09:00 CRDT- 2005/01/07 09:00 PHST- 2005/01/07 09:00 [pubmed] PHST- 2007/03/21 09:00 [medline] PHST- 2005/01/07 09:00 [entrez] PST - ppublish SO - Zhonghua Bing Li Xue Za Zhi. 2004 Dec;33(6):550-4.