Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• The extracellular matrix (ECM) is vital for tissue structure and cell signaling.
• ECM remodeling, regulated by proteolysis, is crucial for development, homeostasis, and disease.
• Proteases are key regulators of ECM structure and function.

Purpose of the Study:

• To review major ECM-degrading protease families and their regulatory mechanisms.
• To highlight shared functions and specialized roles of these proteases.
• To underscore the therapeutic potential of targeting ECM proteolysis.

Main Methods:

• Literature review of ECM-degrading proteases.
• Analysis of protease families: MMPs, serine proteases, ADAMs, ADAMTSs, and cysteine proteases.
• Emphasis on shared regulatory mechanisms and proteolytic activity.

Main Results:

• Protease families exhibit functional redundancy in generating bioactive molecules like matrikines.
• Overlapping substrates and bioactive molecules amplify ECM remodeling.
• Proteases display cell-specific specialization for precise spatiotemporal regulation.
• Dysregulation of ECM proteolysis is linked to pathologies and cancer.

Conclusions:

• Irreversible ECM proteolysis orchestrates complex biological responses in health and disease.
• Targeting ECM proteolysis offers therapeutic potential.
• Understanding protease networks is crucial for regulating biological functions.