Dysregulated proteolytic balance as the basis of excess extracellular matrix in fibrotic disease

Craig A Peters, Michael R. Freeman, Cecilia A. Fernandez, Jennifer Shepard, Dmitri G. Wiederschain, Marsha A. Moses

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

To investigate mechanisms of tissue fibrosis, we developed a model of ovine fetal bladder fibrosis due to surgically induced obstruction. Tissues were analyzed for matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Active MMP-2 was not detected in obstructed bladders, while latent and active forms were detected in normal bladders. MMP-1 (interstitial collagenase) activity was lower in obstructed bladders. MMP inhibitory activity was increased with obstruction, as were levels of TIMP mRNA and protein. These results indicate that the proteins responsible for collagen degradation are present in the developing bladder, and a shift in the proteolytic balance favoring inhibition of degradation occurs in a model of obstruction-induced fibrosis. This altered proteolytic balance favors accumulation of extracellular matrix and decreased tissue compliance characteristic of this and perhaps other fibrotic conditions.

Original languageEnglish (US)
Pages (from-to)R1960-R1965
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume272
Issue number6 41-6
DOIs
StatePublished - 1997

Keywords

  • Bladder
  • Fetal
  • Fibrosis
  • Metalloproteinases
  • Obstruction
  • Tissue inhibitors of metalloproteinases

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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