Extracellular matrix molecules: potential targets in pharmacotherapy

The extracellular matrix (ECM) consists of numerous macromolecules classified traditionally into collagens, elastin, and microfibrillar proteins, proteoglycans including hyaluronan, and noncollagenous glycoproteins. In addition to being necessary structural components, ECM molecules exhibit important functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. Any structural inherited or acquired defect and/or metabolic disturbance in the ECM may cause cellular and tissue alterations that can lead to the development or progression of disease. Consequently, ECM molecules are important targets for pharmacotherapy. Specific agents that prevent the excess accumulation of ECM molecules in the vascular system, liver, kidney, skin, and lung; alternatively, agents that inhibit the degradation of the ECM in degenerative diseases such as osteoarthritis would be clinically beneficial. Unfortunately, until recently, the ECM in drug discovery has been largely ignored. However, several of today's drugs that act on various primary targets affect the ECM as a byproduct of the drugs' actions, and this activity may in part be beneficial to the drugs' disease-modifying properties. In the future, agents and compounds targeting directly the ECM will significantly advance the treatment of various human diseases, even those for which efficient therapies are not yet available.