An integrative view of extracellular matrix ageing
Sylvie RICARD-BLUM
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires,
UMR 5246 CNRS - Université Lyon 1, 43 Boulevard du 11 novembre 1918,
69622 Villeurbanne cedex, France ([email protected])
The extracellular matrix (ECM) determines the shape and the organization of tissues, provides them with mechanical properties, and regulates numerous cellular processes (e.g. proliferation, migration, and differentiation). The ECM is remodeled in diseases such as fibrosis, cancer and diabetes, and in aging, which modulates the release of bioactive fragments called matricryptins. ECM assembly and functions are mediated by protein-protein and protein-glycosaminoglycan interactions, which influence each other and form networks in vivo. We have developed a roadmap to build extracellular interaction networks in order to identify new functions of ECM proteins, and to determine how these interaction networks are rewired at the molecular level in aging and disease with a focus on Alzheimer’s disease. We have created an interaction database, MatrixDB, (http://matrixdb.univ-lyon1.fr) to store ECM interaction data collected experimentally and by manual curation of the literature. We have built an ECM interaction network comprised of ECM and matricellular proteins, proteoglycans, matricryptins, cross-linking (lysyl oxidases, transglutaminase-2, and peroxidasin) and degrading enzymes, and receptors. We now integrate transcriptomics and proteomics data in this network and analyze it with computational tools to determine how it is rewired during aging and if a few proteins connecting different molecular mechanisms (e.g. cross-linking and oxidative stress) play key roles in this process.
Sylvie RICARD-BLUM
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires,
UMR 5246 CNRS - Université Lyon 1, 43 Boulevard du 11 novembre 1918,
69622 Villeurbanne cedex, France ([email protected])
The extracellular matrix (ECM) determines the shape and the organization of tissues, provides them with mechanical properties, and regulates numerous cellular processes (e.g. proliferation, migration, and differentiation). The ECM is remodeled in diseases such as fibrosis, cancer and diabetes, and in aging, which modulates the release of bioactive fragments called matricryptins. ECM assembly and functions are mediated by protein-protein and protein-glycosaminoglycan interactions, which influence each other and form networks in vivo. We have developed a roadmap to build extracellular interaction networks in order to identify new functions of ECM proteins, and to determine how these interaction networks are rewired at the molecular level in aging and disease with a focus on Alzheimer’s disease. We have created an interaction database, MatrixDB, (http://matrixdb.univ-lyon1.fr) to store ECM interaction data collected experimentally and by manual curation of the literature. We have built an ECM interaction network comprised of ECM and matricellular proteins, proteoglycans, matricryptins, cross-linking (lysyl oxidases, transglutaminase-2, and peroxidasin) and degrading enzymes, and receptors. We now integrate transcriptomics and proteomics data in this network and analyze it with computational tools to determine how it is rewired during aging and if a few proteins connecting different molecular mechanisms (e.g. cross-linking and oxidative stress) play key roles in this process.
