title: Deletion of extracellular matrix metalloproteinase inducer/CD147 induces altered cardiac extracellular matrix remodeling in aging mice.
abstract: Extracellular matrix metalloproteinase inducer (EMMPRIN), known for its ability to induce matrix metalloproteinase (MMP) expression, was proposed to play a role in the adverse cardiac extracellular matrix remodeling. After observing an age-associated increase in cardiac EMMPRIN expression in both mice and rats, the role and mechanism of action of EMMPRIN was investigated in the myocardial age-associated changes using 3, 12 and 24 month old EMMPRIN knock-out (KO) vs. wild-type (WT) mice, by cardiac echocardiography, Western blots, immunohistochemistry, ELISA and histology. Adilated cardiomyopathy characterized by a decreased ejection fraction and an enlargement of left ventricular chamber (LV) associated with LV hypertrophy, occurred in KO mice as soon as 12 month old. The increase in interstitial collagen deposition during aging in WT mice could not be detected in KO mice. This may be related to the reduced activation (48% reduction; P < 0.05) and signaling (smad2/3 nuclear translocation) of TGF-β in the 12 month old KO mice which paralleled with a greater reduction in the TGF-β known activating enzymes such as MT1-MMP and MMP-1 (33% and 37% reduction respectively, between 3 and 12 month old in KO mice; P < 0.05) as well as uPA. These findings demonstrate that EMMPRIN gene silencing is associated with an aberrant extracellular matrix remodeling, characterized by the absence of a detected age-associated fibrosis and consequently to dilated cardiopathy, indicating that a fine regulation of EMMPRIN is essential for the coordinated ECM remodeling during aging.
authors.affiliation: Paris-Est University, Laboratory "Croissance Cellulaire, Reparation and Regeneration Tissulaire", CNRS, Creteil, France.|Paris-Est University, INSERM Unit 955, Team 7, Faculty of Medicine, Creteil, France.
authors.forename: E
authors.initials: E
authors.lastname: Huet
authors.affiliation: Paris Diderot University, Sorbonne Paris Cite, and A. de Rothschild Fondation, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Gabison
authors.affiliation: Paris-Est University, Laboratory "Croissance Cellulaire, Reparation and Regeneration Tissulaire", CNRS, Creteil, France.
authors.forename: B
authors.initials: B
authors.lastname: Vallee
authors.affiliation: Pierre and Marie Curie University, Sorbonne Universites, UMS 28 "Phenotypage du petit animal", Faculty of Medicine, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Mougenot
authors.affiliation: Paris-Est University, Laboratory "Croissance Cellulaire, Reparation and Regeneration Tissulaire", CNRS, Creteil, France.
authors.forename: G
authors.initials: G
authors.lastname: Linguet
authors.affiliation: Pierre and Marie Curie University, Sorbonne Universites, INSERM UMR 1166 and Department of Emergency Medicine and Surgery, Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Riou
authors.affiliation: Paris-Est University, Laboratory "Croissance Cellulaire, Reparation and Regeneration Tissulaire", CNRS, Creteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Jarosz
authors.affiliation: Paris-Est University, Laboratory "Croissance Cellulaire, Reparation and Regeneration Tissulaire", CNRS, Creteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Menashi
authors.affiliation: Paris-Est University, Laboratory "Croissance Cellulaire, Reparation and Regeneration Tissulaire", CNRS, Creteil, France. Sophie.Besse@parisdescartes.fr.|Paris-Saclay University, Unit "Biologie Integrative des Adaptations à l'Exercice", INSERM Unit 902, Evry, and Paris-Descartes University, Sorbonne Paris Cite, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Besse
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D051926:Basigin; D003094:Collagen; D020782:Matrix Metalloproteinases