Downregulation of p38 MAPK Involved in Inhibition of LDL-induced Proliferation of Mesangial Cells and Matrix by Curcumin

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 5; pp. 666 - 671
• Main Author: 夏菊梅 张俊 周文祥 刘晓城 韩敏
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2013; Department of Nephrology, the 474th Hospital of PLA, Urumqi 830000, China%Department of Nephrology, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China%Department of Nephrology, Wuhan First Hospital, Wuhan 430022, China%Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Blotting, Western; Cell Proliferation - drug effects; Cells, Cultured; Curcumin - pharmacology; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Dose-Response Relationship, Drug; Down-Regulation; Enzyme Inhibitors - pharmacology; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Gene Expression - drug effects; Imidazoles - pharmacology; LDL; Lipoproteins, LDL - pharmacology; MAPK; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Medicine; Medicine & Public Health; Mesangial Cells - drug effects; Mesangial Cells - metabolism; p38; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; 基质; 增殖抑制; 姜黄素; 肾小球系膜细胞; 诱导系; p38 mitogen activated protein kinase; reactive oxygen species; cyclooxygenase-2; curcumin; low-density lipoprotein
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1178-8

Curcumin, as a main pharmacological component in the traditional Chinese medicine-- tttrmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein （LDL） and different concentrations of curcumin （0, 6.25, 12.5, 25.0 9mol/L） or p38 MAPK inhibitor, SB203580 （10 μmol/L）. Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species （ROS） generation was increased and p38 MAPK was activated significantly （P〈0.05）. When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 μmol/L, LDL-induced proliferation ofmesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated （P〈0.05）. In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS pro- duction and p38 MAPK.