Integrative Models for TGF-β Signaling and Extracellular Matrix

The extracellular matrix (ECM) is the most important regulator of cell-cell communication within tissues. ECM is a complex structure, made up of a wide variety of molecules including proteins, proteglycans and glycoaminoglycans. It contributes to cell signaling through the action of both its constituents and their proteolytic cleaved fragments called matricryptins. In addition, ECM acts as a “reservoir” of growth factors and cytokines and regulates their bioavailability at the cell surface. By controlling cell signaling inputs, ECM plays a key role in regulating cell phenotype (differentiation, proliferation, migration, etc.). In this context, signaling networks associated with the polypeptide transforming growth factor TGF-β are unique since their activation are controlled by ECM and TGF-β is a major regulator of ECM remodeling in return.