Abstract
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.
Highlights
We present a summary of the current literature on the proteolytic imbalance in digestive inflammation focusing on serine proteases and
Serine proteases and matrix metalloproteases (MMPs) are both involved in multiple biological processes such as digestion, immunity, wound healing and inflammatory response, together with their implication in maintaining GI homeostasis
Dysregulation of the proteolytic balance of these two major families of proteases has been linked to digestive inflammation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Recent studies have established the association between increased serine protease activity and IBD pathogenesis [7,8] Due to their implication in tissue remodeling through their ability to degrade extracellular matrix (ECM) components and their immunomodulating effects [9], matrix metalloproteinases (MMPs) are considered key actors of IBD pathogenesis and its related complications such as fistula and fibrosis [10]. The proteolytic activity of serine proteases and MMPs is tightly controlled by their respective protease inhibitors due to their implication in many biological processes. Dysregulation of this balance contributes to IBD pathophysiology [5,11]. We highlight synthetic inhibitors that have reached the clinical trial phase as a candidate for IBD treatment
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