Coordinate regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression in human vascular smooth muscle cells.
The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by human vascular smooth muscle cells (SMC) was monitored as a function of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density. Synthetic phenotype was characterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a maximal level of contractile proteins. Synthetic cells expressed the highest levels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activity. No significant change was detected in MMP-2 expression or catalytic activity. Enzyme immunoassays revealed that MMP-1 expression fell by 77+/-2.4-95+/-0.5%, and that of TIMP-1 by 34+/-0.5-59+/-1.9%, as the cells acquired a contractile phenotype. The level of the MMP-1/TIMP-1 complex was similarly reduced by 78+/-2.9-85+/-1.6%. These data demonstrate that the expression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.
Kato
S
S
Department of Pathology, Kurume University, School of Medicine, 67 Asahi-machi Kurume, 830-0011, Japan. seikato@med.kurume-u.ac.jp
Yasukawa
H
H
Fujii
T
T
Yamaguchi
M
M
Miyagi
N
N
Okamoto
K
K
Wada
Y
Y
Miyamoto
T
T
Morimatsu
M
M
Fox
J C
JC
D000328:Adult; D001011:Aorta; D015153:Blotting, Western; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D017077:Culture Media, Conditioned; D004247:DNA / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D010641:Phenotype; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis; D000097792:Tissue Inhibitor of Metalloproteinase-4
D003094:Collagen; D017364:Collagenases; D017077:Culture Media, Conditioned; D004247:DNA; D020781:Matrix Metalloproteinase 1; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4