Interleukin-1β induces interstitial collagenase gene expression and protein secretion in renal mesangial cells

D. Daphna-Iken, A. R. Morrison

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16 Scopus citations


Degradation and tissue remodeling of the extracellular matrix in the normal glomerulus occur through the coordinate action of neutral metalloproteinases, which are in turn regulated by specific inhibitors. Many of these proteins can be secreted by mesangial cells. In the current study, gene regulation of a rat matrix metalloproteinase, interstitial collagenase and its tissue inhibitor of metalloproteinase-1 (TIMP-1), was investigated by Northern blot analysis. Stimulation of rat mesangial cell (RMC) collagenase by interleukin 1β (IL-1β) produced an increase (>45-fold) in mRNA which peaked at 12 h. Lesser effects on the TIMP-1 mRNA expression were observed in response to IL-1β. Indomethacin did not influence the effect of IL-1β on collagenase, and exogenous prostaglandin E2 had no significant effect either on basal or IL-1β-stimulated mRNA levels. Collagenase was secreted into the media and showed minimal gelatinolytic activity at 36-h stimulation with IL- 1β by zymography. By Western immunoblotting, we demonstrated with 24 h of stimulation the secretion of the active form of collagenase, which further increased after 36 h with IL-1β compared with the control. When RMC were retreated with genistein and herbimycin A, both inhibited collagenase mRNA induction by IL-1β. These data suggest that IL-1β stimulates interstitial collagenase synthesis and activation and that a tyrosine kinase pathway is involved in the signal transduction mechanisms and is not dependent on endogenous prostaglandin biosynthesis. Recently, a third interstitial collagenase (collagenase-3) has been identified from breast carcinoma. This cDNA is 84% identical to the rat interstitial collagenase cDNA probe we have utilized in this study and thus may represent the rat homologue of the human collagenase-3 now called matrix metalloproteinase (MMP)-13.

Original languageEnglish
Pages (from-to)F831-F837
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number6 38-6
StatePublished - 1995


  • interleukin-1
  • interstitial collagenase
  • mesangial cell
  • tyrosine kinase


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