Collagen-modifying enzymes and redox systems

Collagen-modifying enzymes and redox systems represent a complex network of proteins responsible for the maturation, cross-linking, and structural integrity of the extracellular matrix (ECM) [1]. This group includes key enzymes such as prolyl 4-hydroxylases (P4H), lysyl hydroxylases (PLOD), and lysyl oxidases (LOX), which require specific redox conditions and cofactors like iron, copper, and ascorbate to function [2][3]. Redox systems, particularly protein disulfide isomerase (PDI), are integral to this process, acting both as enzymes and chaperones to ensure proper collagen folding within the endoplasmic reticulum [4]. Pathological overactivation of these enzymes leads to excessive collagen deposition and stiffening, which are hallmarks of organ fibrosis and the tumor microenvironment, where they facilitate cancer cell invasion and metastasis [5][6]. Therapeutic targeting of these systems, such as through LOX inhibitors or redox modulators, aims to halt fibrotic progression and sensitize tumors to treatment, although achieving tissue specificity remains a significant challenge [7]. Monitoring biomarkers like hydroxyproline or LOX expression is essential for evaluating treatment efficacy in clinical settings [8].

Other names

ECM-modifying enzymesCollagen processing enzymesCollagen biosynthetic pathwayCollagen hydroxylases and oxidases

Inhibition of lysyl oxidase-mediated cross-linking, suppression of prolyl and lysyl hydroxylation, and modulation of the redox environment to disrupt collagen maturation and extracellular matrix stability.