Production of tissue collagenase (matrix metalloproteinase 1) by human aortic smooth muscle cells in response to platelet-derived growth factor.
The production of the precursor of tissue collagenase/matrix metalloproteinase 1 (proMMP-1) by cultured human aortic medial smooth muscle cells (SMCs) was significantly enhanced by the treatment of the cells with platelet-derived growth factor (PDGF), interleukin 1 or 12-O-tetradecanoylphorbol-13-acetate (TPA). The response to PDGF of SMCs exhibited a tendency to be age-dependent: only SMCs obtained from older individuals (age: 54, 56, 72 and 74 years) responded to PDGF and synthesized proMMP-1, but not SMCs from young individuals (age: 10, 16 and 41 years), and weak responsiveness with a 19-year-old individual. On the other hand, induction of proMMP-1 synthesis in SMCs by TPA was not discriminated by age. The synthesis of two other related matrix metalloproteinases was also examined. Matrix metalloproteinase 2 was found to be constitutively expressed in zymogen form in SMCs and its synthesis was not affected by the treatments with PDGF, interleukin 1 or TPA. The synthesis of matrix metalloproteinase 3 (stromelysin) was not detected in SMCs from both young and old individuals even after the treatment with PDGF, interleukin-1, prostaglandin E2 or TPA. The ability of SMCs to synthesize and secrete proMMP-1 in response to PDGF suggests that this enzyme plays an important role in the migration of PDGF-stimulated SMCs from the media into the intima of aorta and the eventual formation of atherosclerotic plaques.
Yanagi
H
H
Second Department of Pathology, Kurume University School of Medicine, Japan.
Sasaguri
Y
Y
Sugama
K
K
Morimatsu
M
M
Nagase
H
H
D000293:Adolescent; D000368:Aged; D000375:Aging / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D004792:Enzyme Precursors / Q000096:biosynthesis; D005260:Female; D018093:Gelatinases; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis; D003012:Microbial Collagenase / Q000096:biosynthesis*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010434:Pepsin A / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*
D004792:Enzyme Precursors; D010982:Platelet-Derived Growth Factor; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D019278:Matrix Metalloproteinase 3; D003012:Microbial Collagenase; D020781:Matrix Metalloproteinase 1