Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, France.
Department of Clinical Sciences, Nantes-Atlantic College of Veterinary Medicine and Food Sciences (Oniris), University of Nantes, 101 Route de Gachet, 44300 Nantes, France.
Int J Mol Sci. 2021 Mar 10;22(6):2817. doi: 10.3390/ijms22062817.
Dysregulation of the proteolytic balance is often associated with diseases. Serine proteases and matrix metalloproteases are involved in a multitude of biological processes and notably in the inflammatory response. Within the framework of digestive inflammation, several studies have stressed the role of serine proteases and matrix metalloproteases (MMPs) as key actors in its pathogenesis and pointed to the unbalance between these proteases and their respective inhibitors. Substantial efforts have been made in developing new inhibitors, some of which have reached clinical trial phases, notwithstanding that unwanted side effects remain a major issue. However, studies on the proteolytic imbalance and inhibitors conception are directed toward host serine/MMPs proteases revealing a hitherto overlooked factor, the potential contribution of their bacterial counterpart. In this review, we highlight the role of proteolytic imbalance in human digestive inflammation focusing on serine proteases and MMPs and their respective inhibitors considering both host and bacterial origin.
蛋白酶平衡失调通常与疾病有关。丝氨酸蛋白酶和基质金属蛋白酶参与了多种生物过程，特别是在炎症反应中。在消化炎症的框架内，有几项研究强调了丝氨酸蛋白酶和基质金属蛋白酶 (MMPs) 在其发病机制中的关键作用，并指出了这些蛋白酶与其各自抑制剂之间的不平衡。尽管存在不良副作用等问题，但人们在开发新抑制剂方面做出了巨大努力，其中一些已进入临床试验阶段。然而，对蛋白酶失衡和抑制剂概念的研究主要针对宿主丝氨酸/MMPs 蛋白酶，揭示了一个迄今为止被忽视的因素，即其细菌对应物的潜在贡献。在这篇综述中，我们强调了蛋白酶失衡在人类消化炎症中的作用，重点关注丝氨酸蛋白酶和 MMPs 及其各自的抑制剂，同时考虑了宿主和细菌的来源。
