title: Involvement of matrix metalloproteinases (MMPs) and inflammasome pathway in molecular mechanisms of fibrosis.
abstract: 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.
authors.affiliation: UMR991 INSERM, Université de Rennes 1, 35043 Rennes, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Robert
authors.affiliation: UMR991 INSERM, Université de Rennes 1, 35043 Rennes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gicquel
authors.affiliation: Laboratório de Reparo Tecidual, DHE/IBRAG/UERJ, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Victoni
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Valença
authors.affiliation: Laboratory of Cell Biology, Federal University of Alagoas, 57072-900 Maceió-AL, Brazil.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Barreto
authors.affiliation: INSERM, U1065, Faculté de Médecine, Université de Nice Sophia Antipolis, 06204 Nice, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bailly-Maître
authors.affiliation: UMR991 INSERM, Université de Rennes 1, 35043 Rennes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Boichot
authors.affiliation: UMR991 INSERM, Université de Rennes 1, 35043 Rennes, France vincent.lagente@univ-rennes1.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lagente
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases
keywords: fibrosis; inflammasome; interleukin-1; liver; lung; matrix metalloproteinase; purinergic receptors; tissue inhibitors of metalloproteinase (TIMP)-1