title: Involvement of integrins, MAPK, and NF-kappaB in regulation of the shear stress-induced MMP-9 expression in endothelial cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Sun
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Li
authors.forename: Huai-Qing
authors.initials: HQ
authors.lastname: Chen
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Lin
authors.forename: Hui-Xia
authors.initials: HX
authors.lastname: Lv
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: 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
chemical_list: D016023:Integrins; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9