Small mechanical strains selectively suppress matrix metalloproteinase-1 expression by human vascular smooth muscle cells

被引:64
作者
Yang, JH [1 ]
Briggs, WH [1 ]
Libby, P [1 ]
Lee, RT [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA
关键词
D O I
10.1074/jbc.273.11.6550
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mechanical forces and biochemical stimuli may interact to regulate cellular responses, In this study, we tested the hypothesis that very small mechanical strains interact with growth factors in the regulation of matrix metalloproteinase (MMP)-1. Human vascular smooth muscle cells (VSMCs) were cultured on a precoated silicone membrane in a device that imposes a highly uniform biaxial strain, VSMCs cultured on fibronectin were treated with cyclic 1-Hz strains of 0, 1, or 4%, and MMPs were assayed by Western analysis or gelatin zymography. Small strains did not induce MMP-1 in VSMCs, but strain was a potent inhibitor of platelet-derived growth factor (PDGF)- or tumor necrosis factor-alpha-induced synthesis of MMP-1. In contrast, MMP-2 and TIMP-2 levels were not changed by PDGF and/or mechanical strain. VSMCs strained on the 120-kDa chymotryptic fragment of fibronectin or RGD peptides suppressed PDGF-induced expression of MMP-1, indicating that this effect is not mediated by the heparin-binding domain or connecting segment-1 of fibronectin. Northern analysis of ets-1, a transcriptional activator of MMP-1 expression, showed that strain down-regulated ets-1 expression, whereas c-fos expression was augmented. Thus, small deformations can selectively suppress MMP-1 synthesis by VSMCs, demonstrating the exquisite sensitivity of the cell to mechanical stimuli.
引用
收藏
页码:6550 / 6555
页数:6
相关论文
共 43 条
  • [1] UV IRRADIATION AND HEAT-SHOCK MEDIATE JNK ACTIVATION VIA ALTERNATE PATHWAYS
    ADLER, V
    SCHAFFER, A
    KIM, J
    DOLAN, L
    RONAI, Z
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (44) : 26071 - 26077
  • [2] The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA-dependent and -independent manner
    Basuyaux, JP
    Ferreira, E
    Stehelin, D
    Buttice, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (42) : 26188 - 26195
  • [3] PROLONGED ACTIVATION OF JUN AND COLLAGENASE GENES BY TUMOR NECROSIS FACTOR-ALPHA
    BRENNER, DA
    OHARA, M
    ANGEL, P
    CHOJKIER, M
    KARIN, M
    [J]. NATURE, 1989, 337 (6208) : 661 - 663
  • [4] Buttice G, 1996, ONCOGENE, V13, P2297
  • [5] Autocrine induction of DNA synthesis by mechanical injury of cultured smooth muscle cells - Potential role of FGF and PDGF
    Calara, F
    Ameli, S
    HultgardhNilsson, A
    Cercek, B
    Kupfer, J
    Hedin, U
    Forrester, J
    Shah, PK
    Nilsson, J
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (02) : 187 - 193
  • [6] Mechanical strain tightly controls fibroblast growth factor-2 release from cultured human vascular smooth muscle cells
    Cheng, GC
    Briggs, WH
    Gerson, DS
    Libby, P
    Grodzinsky, AJ
    Gray, ML
    Lee, RT
    [J]. CIRCULATION RESEARCH, 1997, 80 (01) : 28 - 36
  • [7] SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION
    CHOMCZYNSKI, P
    SACCHI, N
    [J]. ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) : 156 - 159
  • [8] JNK1 - A PROTEIN-KINASE STIMULATED BY UV-LIGHT AND HA-RAS THAT BINDS AND PHOSPHORYLATES THE C-JUN ACTIVATION DOMAIN
    DERIJARD, B
    HIBI, M
    WU, IH
    BARRETT, T
    SU, B
    DENG, TL
    KARIN, M
    DAVIS, RJ
    [J]. CELL, 1994, 76 (06) : 1025 - 1037
  • [9] CYTOKINE-STIMULATED HUMAN VASCULAR SMOOTH-MUSCLE CELLS SYNTHESIZE A COMPLEMENT OF ENZYMES REQUIRED FOR EXTRACELLULAR-MATRIX DIGESTION
    GALIS, ZS
    MUSZYNSKI, M
    SUKHOVA, GK
    SIMONMORRISSEY, E
    UNEMORI, EN
    LARK, MW
    AMENTO, E
    LIBBY, P
    [J]. CIRCULATION RESEARCH, 1994, 75 (01) : 181 - 189
  • [10] INCREASED EXPRESSION OF MATRIX METALLOPROTEINASES AND MATRIX-DEGRADING ACTIVITY IN VULNERABLE REGIONS OF HUMAN ATHEROSCLEROTIC PLAQUES
    GALIS, ZS
    SUKHOVA, GK
    LARK, MW
    LIBBY, P
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (06) : 2493 - 2503