Involvement of matrix metalloproteinases (MMPs) and inflammasome pathway in molecular mechanisms of fibrosis

Sacha Robert, Thomas Gicquel, Tatiana Victoni, Samuel Valença, Emiliano Barreto, Béatrice Bailly-Maître, Elisabeth Boichot, Vincent Lagente

Research output: Contribution to journalReview articlepeer-review

144 Scopus citations


Fibrosis is a basic connective tissue lesion defined by the increase in the fibrillar extracellular matrix (ECM) components in tissue or organ. Matrix metalloproteinases (MMPs) are a major group of proteases known to regulate the turn-over of ECM and so they are suggested to be important in tissue remodelling observed during fibrogenic process associated with chronic inflammation. Tissue remodelling is the result of an imbalance in the equilibrium of the normal processes of synthesis and degradation of ECM components markedly controlled by the MMPs/TIMP imbalance. We previously showed an association of the differences in collagen deposition in the lungs of bleomycin-treated mice with a reduced molar pro-MMP-9/TIMP-1 ratio. Using the carbon tetrachloride (CCl4) preclinical model of liver fibrosis in mice, we observed a significant increase in collagen deposition with increased expression and release of tissue inhibitors of metalloproteinase (TIMP)-1 both at 24 h and 3 weeks later. This suggests an early altered regulation of matrix turnover involved in the development of fibrosis. We also demonstrated an activation of NLRP3-inflammasome pathway associated with the IL-1R/MyD88 signalling in the development of experimental fibrosis both in lung and liver. This was also associated with an increased expression of purinergic receptors mainly P2X7. Finally, these observations emphasize those effective therapies for these disorders must be given early in the natural history of the disease, prior to the development of tissue remodelling and fibrosis.

Original languageEnglish (US)
Article numbere00360
JournalBioscience Reports
Issue number4
StatePublished - Aug 1 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 The Author(s).


  • Fibrosis
  • Inflammasome
  • Interleukin-1
  • Liver
  • Lung
  • Matrix metalloproteinase
  • Purinergic receptors
  • Tissue inhibitors of metalloproteinase (TIMP)-1


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