Gastric pathology and metalloproteinases

Abstract

The spectrum of gastric pathologies involves heterogeneity with respect tobiochemical mechanisms and clinical outcome and is globally common. Eachyear, 5-6 million people worldwide are affected by gastric ulcer, gastric cancerand inflammatory bowel diseases, and mortality rate being >50% shows steepincrease in incidence. Hence, understanding the underlying pathogenesis andbetter therapeutic strategies remain the major challenges in gastroenterologyfield. Current knowledge of gastric pathology reveals that extracellular proteasesvastly influence functional irregularities of cells along with their responses tomicroenvironment. Based on studies on metalloproteinases and their inhibitors, it is well accepted about their important roles in physiological developmentalprocesses as well as pathological conditions. From past several years ofextensive research on matrix, metalloproteinases (MMPs) establish their criticalrole in several cellular functions including proliferation, apoptosis and angiogenesis. MMPs are a family of "molecular scissors" with ambivalent actions andability to cleave extracellular matrix (ECM) proteins that in turn facilitate tissueremodelling. Approximately, 27 subtypes of MMPs are there having mutualinteraction among each of them in gastrointestinal disorders. Functional overlapbetween the MMPs leads to non-specificity, which makes designing MMPinhibitors more difficult. Thus, specific MMP inhibitors would be promisingtherapeutic tool against inflammatory diseases including gastric diseases. Thischapter illustrates the new insights into mechanism of MMP regulation in gastrointestinal inflammatory disorders encompassing clinical trials for MMPinhibitors and new therapeutic strategies by targeting specific MMP(s) to controlgastrointestinal pathologies.