Endogenous extracellular matrix molecules (ECM)

The endogenous extracellular matrix (ECM) is a complex, non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans, glycosaminoglycans, and glycoproteins that provide essential structural and biochemical support to tissues (Frantz et al., 2010, J Cell Sci). Beyond its role as a physical scaffold, the ECM acts as a dynamic signaling hub, regulating cell behavior such as proliferation, migration, and differentiation through interactions with cell-surface receptors like integrins (Hynes, 2009, Science). In various diseases, the ECM undergoes pathological remodeling; for instance, excessive deposition of collagen leads to organ fibrosis, while the degradation of matrix components by enzymes like matrix metalloproteinases (MMPs) facilitates tumor invasion and metastasis (Lu et al., 2012, J Cell Biol). Pharmacological targeting of the ECM is a diverse field, ranging from the use of enzymatic agents like collagenase clostridium histolyticum to treat Dupuytren's contracture to the application of hyaluronidase to increase tissue permeability for drug delivery (Hurst et al., 2009, N Engl J Med; Bookbinder et al., 2006, J Control Release). Additionally, exogenous ECM molecules like hyaluronic acid and chondroitin sulfate are utilized as viscosupplements in the management of osteoarthritis (Bannuru et al., 2019, Ann Intern Med). While the ECM presents a rich landscape for therapeutic intervention, its ubiquitous presence in the body necessitates high specificity to avoid adverse effects on normal tissue architecture and the body's natural repair mechanisms.

Other names

Extracellular matrixECM componentsMatrisomeIntercellular matrixConnective tissue matrix

Therapeutic strategies involve the enzymatic degradation of accumulated matrix components (e.g., collagen or hyaluronan), the inhibition of cross-linking enzymes such as lysyl oxidase-like 2 (LOXL2) to prevent matrix stiffening, or the use of exogenous ECM components to restore tissue lubrication and integrity.