Antalis Toni M, Shea-Donohue Terez, Vogel Stefanie N, Sears Cynthia, Fasano Alessio
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Nat Clin Pract Gastroenterol Hepatol. 2007 Jul;4(7):393-402. doi: 10.1038/ncpgasthep0846.
Of all our organ systems, the gastrointestinal tract contains the highest levels of endogenous and exogenous proteases (also known as proteinases and peptidases); however, our understanding of their functions and interactions within the gastrointestinal tract is restricted largely to nutrient digestion. The gut epithelium is a sensor of the luminal environment, not only controlling digestive, absorptive and secretory functions, but also relaying information to the mucosal immune, vascular and nervous systems. These functions involve a complex array of cell types that elaborate growth factors, cytokines and extracellular matrix (ECM) proteins, the activity and availability of which are regulated by proteases. Proteolytic activity must be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological gastrointestinal conditions. Moreover, enteric microbes and parasites can hijack proteolytic pathways through 'pathogen host mimicry'. Understanding how the protease balance is maintained and regulated in the intestinal epithelial cell microenvironment and how proteases contribute to physiological and pathological outcomes will undoubtedly contribute to the identification of new potential therapeutic targets for gastrointestinal diseases.
在我们所有的器官系统中，胃肠道所含的内源性和外源性蛋白酶（也称为蛋白酶和肽酶）水平最高；然而，我们对它们在胃肠道内的功能及相互作用的了解，很大程度上局限于营养物质的消化。肠道上皮是管腔环境的传感器，不仅控制消化、吸收和分泌功能，还向黏膜免疫、血管和神经系统传递信息。这些功能涉及一系列复杂的细胞类型，它们会分泌生长因子、细胞因子和细胞外基质（ECM）蛋白，而这些蛋白的活性和可利用性受蛋白酶调控。面对各种环境挑战时，蛋白水解活性必须受到严格调控，因为不受控制或过度的蛋白水解会导致胃肠道疾病。此外，肠道微生物和寄生虫可通过“病原体宿主模拟”来利用蛋白水解途径。了解肠道上皮细胞微环境中蛋白酶平衡是如何维持和调控的，以及蛋白酶如何影响生理和病理结果，无疑将有助于确定胃肠道疾病新的潜在治疗靶点。
