Abstract
Substance P is involved in inflammatory processes, but its effect on extracellular matrix metabolism has not been studied; therefore, the authors evaluated its effect on collagen synthesis and degradation, expression of pro-alpha1(I) collagen, matrix metalloproteinase-1 and -2, and tissue inhibitor of metalloproteinase-1 and -2 in normal human lung fibroblast strains. Substance P induced a decrease in collagen biosynthesis, concomitant to a down-regulation of pro-alpha1(I) collagen mRNA. In contrast, an increase in collagen degradation was observed, accompanied with an up-regulation of matrix metalloproteinase-1. Substance P did not influence tissue inhibitor of metalloproteinase-1 and -2 or matrix metalloproteinase-2 expression. The results suggest that substance P participates in extracellular matrix metabolism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Cell Proliferation
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Cells, Cultured
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Child, Preschool
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Collagen / genetics
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Collagen / metabolism*
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Collagen Type I / metabolism
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Dose-Response Relationship, Drug
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Down-Regulation
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Enzyme Induction
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Female
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Fibroblasts / metabolism*
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Humans
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Lung / drug effects
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Lung / enzymology
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Lung / metabolism*
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Lung / pathology
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Male
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Matrix Metalloproteinase 1 / biosynthesis*
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Matrix Metalloproteinase 1 / genetics
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Neurokinin-1 Receptor Antagonists
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RNA, Messenger / metabolism
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Receptors, Neurokinin-1 / metabolism
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Substance P / metabolism*
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Substance P / pharmacology
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Tryptophan / analogs & derivatives
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Tryptophan / pharmacology
Substances
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Collagen Type I
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Neurokinin-1 Receptor Antagonists
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RNA, Messenger
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Receptors, Neurokinin-1
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3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan
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Substance P
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Tryptophan
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Collagen
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Matrix Metalloproteinase 1