Involvement of integrins, MAPK, and NF-kappaB in regulation of the shear stress-induced MMP-9 expression in endothelial cells.
Variations in the matrix metalloproteinase (MMP)-9 gene are related to the presence and severity of atherosclerosis. The aim of this study was to determine the signaling pathways of MMP-9 in endothelial cells subjected to low fluid shear stress. We found that low fluid shear stress significantly increased MMP-9 expression, IkappaBalpha degradation, NF-kappaB DNA-binding activity and phosphorylation of MAPK in cultured human umbilical vein endothelial cells (HUVECs). Inhibition of NF-kappaB resulted in remarkable downregulation of stress-induced MMP-9 expression. Pretreatment of HUVECs with inhibitors of p38 mitogen-activating protein kinase (MAPK) and extracellular signal-regulated kinase1/2 (ERK1/2) also led to significant suppression of stress-induced MMP-9 expression and NF-kappaB DNA-binding activity. Similarly, addition of integrins inhibitor to HUVECs suppressed the stress-induced MMP-9 expression, IkappaBalpha degradation, NF-kappaB DNA-binding activity and the phosphorylation of p38 MAPK, ERK1/2. Our findings demonstrated that the shear stress-induced MMP-9 expression involved integrins-p38 MAPK or ERK1/2-NF-kappaB signaling pathways.
Sun
Hui-Wen
HW
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, PR China.
Li
Chang-Jiang
CJ
Chen
Huai-Qing
HQ
Lin
Hui-Li
HL
Lv
Hui-Xia
HX
Zhang
Yun
Y
Zhang
Mei
M
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D033081:Shear Strength; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical
D016023:Integrins; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9