Substance P up-regulates matrix metalloproteinase-1 and down-regulates collagen in human lung fibroblast

Exp Lung Res. 2007 Apr-May;33(3-4):151-67. doi: 10.1080/01902140701364409.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Proliferation
  • Cells, Cultured
  • Child, Preschool
  • Collagen / genetics
  • Collagen / metabolism*
  • Collagen Type I / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Enzyme Induction
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism*
  • Humans
  • Lung / drug effects
  • Lung / enzymology
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • Neurokinin-1 Receptor Antagonists
  • RNA, Messenger / metabolism
  • Receptors, Neurokinin-1 / metabolism
  • Substance P / metabolism*
  • Substance P / pharmacology
  • Tryptophan / analogs & derivatives
  • Tryptophan / pharmacology

Substances

  • Collagen Type I
  • Neurokinin-1 Receptor Antagonists
  • RNA, Messenger
  • Receptors, Neurokinin-1
  • 3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan
  • Substance P
  • Tryptophan
  • Collagen
  • Matrix Metalloproteinase 1