Extracellular matrix proteoglycans and collagens (ECM)

The extracellular matrix (ECM) proteoglycans and collagens constitute the primary structural framework of all tissues, providing mechanical support and biochemical cues to resident cells (Frantz et al., 2010, Journal of Cell Science). Collagens, the most abundant proteins in the human body, provide tensile strength, while proteoglycans, characterized by their glycosaminoglycan chains, regulate tissue hydration and sequester growth factors (Iozzo & Schaefer, 2015, FEBS Journal). In pathological states such as fibrosis and cancer, the dysregulation of these components leads to excessive tissue hardening or the creation of a pro-tumorigenic microenvironment (Winkler et al., 2020, Nature Communications). Therapeutic strategies targeting the ECM include the use of collagenases like Collagenase clostridium histolyticum to dissolve excessive fibrous tissue in conditions like Dupuytren's contracture (Hurst et al., 2009, NEJM). Additionally, anti-fibrotic drugs like Pirfenidone and Nintedanib work by modulating the pathways that lead to excessive collagen deposition (Noble et al., 2011, The Lancet). Modifying the ECM is also a critical approach in oncology to enhance the penetration of chemotherapeutic agents into dense solid tumors (Oliver et al., 2023, Frontiers in Oncology).

Other names

Extracellular matrix componentsConnective tissue proteinsGround substanceFibrillar collagensSmall leucine-rich proteoglycans (SLRPs)

The primary mechanisms of action include the enzymatic degradation of collagen or hyaluronan to reduce tissue stiffness, the inhibition of TGF-beta or other profibrotic signaling pathways to decrease the synthesis of new ECM components, and the inhibition of enzymes like lysyl oxidase (LOX) to prevent the cross-linking and stabilization of the matrix (Winkler et al., 2020, Nature Communications).