Axis 3: Aging and Tissue Repair: "The Role of Extracellular Matrix in Cell Differentiation. Involvement in aging and repair of arterial tissue, skin and bone

Coordinators: Z.MASSY (UPJV) and D.LAURENT-MAQUIN (URCA)

Participating Teams: INSERM UMRS 1088, URMS INSERM 903, CNRS FRE 3481, EA 3801, CNRS FRE 3517 (team THERA), CNRS UMR 7312, EA 4691

The project of this axis is to study the cell-microenvironment interactions in aging and tissue repair and to analyze the cellular and molecular responses to various components of the extracellular matrix. Whithin this framework, the mechanisms of differentiation of a cell as a component of a tissue or organ, permitting either remodeling, wound healing or tissue regeneration, the orientation of the system toward a pathological situation will be considered.
The research program of this axis has four major themes:
1. Involvement of calcium-sensing receptor (CaSR) and elastin receptor complex (S-Gal/cathA/neu-1) in arterial and bone remodeling ;
2. Angiogenesis and bone bioengineering;
3. Skin aging and post-translational modifications of the extracellular matrix;
4. Design, isolation and synthesis of pharmacological agents.

This project involves several teams from UPJV and URCA, in conjunction whith clinical services of the University Hospitals of Amiens and Reims. These teams have developed a recognized expertise in the areas of arterial tissue, skin and bone remodeling, and some have previously collaborated on a common research program dedicated to the extracellular matrix. It aims to: (1) study the changes of the cellular microenvironment, including that consecutive to the activation of proteolytic cascades and their implications for the mechanisms of activation and regulation of cell differentiation and tissue repair during aging and (2) elaborate biomatrices from bone and vascular bioengineering, (3) design, synthesize and isolate pharmacological agents.
For the sake of strong thematic focus, the entire project is specifically focused on the role of matrix metalloproteinases and matrikines ( bioactive degradation products of the matrix) in the mechanisms of arteries, skin and bone remodeling. This approach is based on the availability within partner teams of several in vitro and in vivo highly original models which permit the analysis of tissue remodeling. It also beneficiates of the availability of innovative functional imaging technologies of living cells, of the contribution of infrared and Raman spectroscopies for tissue analysis, and of the involvement of teams specialized in molecular modeling, design and production of new pharmacological agents.