Extracellular matrix secretion and deposition pathways

The extracellular matrix (ECM) secretion and deposition pathways encompass the complex series of intracellular and extracellular events responsible for the synthesis, transport, and assembly of structural proteins and glycoconjugates that form the tissue scaffold (Naba et al., 2012, Molecular & Cellular Proteomics). This process begins with the translation of ECM precursors like procollagen in the endoplasmic reticulum, followed by post-translational modifications, Golgi-mediated secretion, and final extracellular assembly and cross-linking (Canty & Kadler, 2005, Journal of Cell Science). Once extracellular, these components are organized into complex scaffolds through enzymatic cross-linking, primarily mediated by the lysyl oxidase (LOX) family, and interactions with cell-surface receptors like integrins (Cox & Erler, 2011, Disease Models & Mechanisms). Pathological over-activation of these pathways leads to fibrosis in organs such as the lungs, liver, and kidneys, characterized by excessive scarring and loss of function (Wynn, 2008, Journal of Pathology). In oncology, an aberrant ECM creates a pro-tumorigenic microenvironment that facilitates invasion, metastasis, and drug resistance (Lu et al., 2011, Journal of Cell Biology). Therapeutic strategies targeting these pathways often focus on inhibiting key regulatory cytokines like TGF-beta or specific enzymes like lysyl oxidase (LOX) that stabilize the matrix (Frantz et al., 2010, Journal of Cell Science). However, because the ECM is vital for normal tissue integrity and wound repair, pharmacological intervention requires precise targeting to avoid adverse effects such as impaired healing or vascular fragility (Frantz et al., 2010, Journal of Cell Science).

Other names

Extracellular matrix assemblyECM biogenesisFibrogenesis pathwaysMatrisome secretion and assembly

Inhibition of pro-fibrotic signaling (e.g., TGF-beta), inhibition of matrix cross-linking enzymes (e.g., LOXL2), inhibition of receptor tyrosine kinases involved in fibroblast proliferation, and enzymatic degradation of existing matrix components like hyaluronan.