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Published on: May 21, 2021
Regulation of meprin metalloproteases in mucosal homeostasis
Ludwig Werny1, Cynthia Colmorgen1, Christoph Becker-Pauly1
1Biochemical Institute, Unit for Degradomics of the Protease Web, University of Kiel, Kiel, Germany.
Abstract:
Mucus is covering the entire epithelium of the gastrointestinal tract (GIT), building the interface for the symbiosis between microorganisms and their host. Hence, a disrupted mucosal barrier or alterations of proper mucus composition, including the gut microbiota, can cause severe infection and inflammation. Meprin metalloproteases are well-known to cleave various pro-inflammatory molecules, contributing to the onset and progression of pathological conditions including sepsis, pulmonary hypertension or inflammatory bowel disease (IBD). Moreover, meprins have an impact on migration and infiltration of immune cells like monocytes or leukocytes during intestinal inflammation by cleaving tight junction proteins or cell adhesion molecules, thereby disrupting epithelial cell barrier and promoting transendothelial cell migration. Interestingly, both meprin α and meprin β are susceptibility genes for IBD. However, both genes are significantly downregulated in inflamed intestinal tissue in contrast to healthy donors. Therefore, a detailed understanding of the underlying molecular mechanisms is the basis for developing new and effective therapies against manifold pathologies like IBD. This review focuses on the regulation of meprin metalloproteases and its impact on physiological and pathological conditions related to mucosal homeostasis.
Insights
Meprin metalloproteases regulate the gut mucosal barrier, impacting inflammatory bowel disease (IBD). Understanding their regulation is key to developing new therapies for IBD and other inflammatory conditions.
Area of Science:
- Gastroenterology and Immunology
- Molecular Biology
Background:
- The gastrointestinal tract (GIT) is lined by mucus, crucial for host-microbe symbiosis.
- Disrupted mucosal barriers or altered mucus composition can lead to infection and inflammation.
- Meprin metalloproteases cleave pro-inflammatory molecules and affect immune cell migration, impacting diseases like inflammatory bowel disease (IBD).
Purpose of the Study:
- To review the regulation of meprin metalloproteases.
- To understand the impact of meprins on mucosal homeostasis in physiological and pathological conditions.
- To explore meprin's role in inflammatory bowel disease (IBD).
Main Methods:
- Literature review focused on meprin metalloproteases.
- Analysis of meprin's role in mucosal barrier function.
- Examination of meprin's involvement in immune cell migration and inflammatory processes.
Main Results:
- Meprin α and meprin β are identified as susceptibility genes for IBD.
- Meprin expression is significantly downregulated in inflamed intestinal tissue compared to healthy tissue.
- Meprin metalloproteases influence immune cell infiltration by cleaving cell adhesion and tight junction proteins.
Conclusions:
- Meprin metalloproteases play a complex role in mucosal homeostasis and inflammation.
- Dysregulation of meprins contributes to pathological conditions like IBD.
- Further understanding of meprin regulation is essential for developing novel therapeutic strategies for IBD.
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