An update on the landscape of collagen bioactive fragments

Extracellular matrix (ECM) proteins, known as the matrisome, have long been recognized for their structural roles and their control of cell phenotypes in health and disease. The broad range of biological activities mediated by the ECM has been further expanded with the discovery that fragments released upon ECM remodeling are also bioactive with functions that can differ from those of their parent proteins. This review provides an overview of the latest findings describing the roles of major bioactive fragments from collagens I, IV, VI, and XVIII in various physiological and pathological contexts affecting heart, lung, adipose, and even brain tissues. Angiogenesis, inflammation, fibrosis, and cancer are the most frequent processes regulated by collagen fragments. Perspectives on how these bioactive fragments could impact translational research as drug candidates, drug targets, and biomarkers are also discussed together with their biomedical applications.