Molecular Biology of the Plasminogen System: The Delicate Balance between Tissue Healing and Tissue Destruction

Proteinases play a central role in the complex response of tissues to injury by influencing cellular behavior and matrix remodeling. Considerable information on the biology of proteinases has been derived from gene targeting and gene transfer studies. One of the best characterised proteinase systems is the plasminogen system, belonging to the large serine proteinase family. Using mice with a targeted deficiency of plasminogen system components, it has become obvious that the plasminogen system can — directly or indirectly by activation of matrix metalloproteinases — have divergent — even opposite — roles in disease favoring healing in some cases and promoting tissue destruction in others. This Chapter discusses the mechanisms by which the plasminogen system can influence the response to injury in the vessel wall, the heart, the nervous system, the lungs and the skin.