Collagen synthesis and extracellular matrix remodeling pathways (ECM remodeling pathways)

Collagen synthesis and extracellular matrix (ECM) remodeling pathways encompass the complex biochemical processes responsible for the production, modification, and degradation of the structural scaffold surrounding cells (Lu, P., et al., 2012, Journal of Cell Biology). These pathways involve a variety of enzymes, such as lysyl oxidases and matrix metalloproteinases, as well as signaling molecules like transforming growth factor-beta (TGF-beta) that regulate fibroblast activity (Meng, X. M., et al., 2016, Nature Reviews Nephrology). In healthy tissues, these processes maintain structural integrity and facilitate repair; however, dysregulation leads to pathological conditions such as fibrosis, where excessive collagen accumulation impairs organ function, or cancer, where ECM remodeling promotes tumor invasion and metastasis (Walker, C., et al., 2018, Journal of Pathology). Therapeutic strategies often focus on inhibiting the overactive signaling or enzymatic activity that drives collagen deposition, with drugs like pirfenidone and nintedanib used to treat idiopathic pulmonary fibrosis (Noble, P. W., et al., 2011, The Lancet; Richeldi, L., et al., 2014, New England Journal of Medicine). While targeting these pathways holds promise for treating chronic fibroproliferative diseases, challenges include achieving tissue specificity and avoiding the disruption of essential physiological wound healing and tissue maintenance (Nielsen, M. J., et al., 2019, Journal of Hepatology).

Other names

Extracellular matrix remodelingCollagen biosynthesisECM turnoverFibrotic signaling pathways

Drugs targeting these pathways typically act by inhibiting pro-fibrotic cytokines like TGF-beta, blocking tyrosine kinase receptors involved in fibroblast activation, or modulating the activity of matrix metalloproteinases (MMPs) to prevent excessive collagen deposition and promote matrix degradation (Meng, X. M., et al., 2016, Nature Reviews Nephrology; Noble, P. W., et al., 2011, The Lancet).