Extracellular matrix cross‐talk with proteases: A master switch for remodeling and cell regulation in health and disease

The extracellular matrix (ECM) is a dynamic three-dimensional macromolecular network essential for maintaining tissue homeostasis. Apart from its structural and biomechanical support to tissues, the ECM plays regulatory roles in cellular signaling, cell functional properties, and morphology. The composition and structural characteristics of the ECM are widely variable among different tissues, adapting to diverse functional needs. The extensive and dysregulated remodeling of the ECM network in various diseases-such as cancer, fibrosis, and vascular and inflammatory conditions-influences their progression. ECM remodeling involves not only proteolytic degradation but also the deposition of newly synthesized matrix components that influence cellular behavior. In this special issue on ECM cross-talk with proteases, the categories and functions of various proteases are presented and discussed in terms of their involvement in ECM remodeling and cell regulatory effects. Emphasis is placed on the roles of matrix metalloproteinases (MMPs), cathepsins, a disintegrin and metalloproteinase (ADAM), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), components of the plasminogen activation system, and lysyl oxidase (LOX) family enzymes-both in the degradation of ECM macromolecules (collagen, elastic fibers, proteoglycans) and in their impact on extracellular vesicles (EVs) and microRNAs (miRNAs).