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Pubmed- Regulation of meprin metalloproteases in mucosal homeostasis


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Posted 10 October 2021 - 07:25 AM

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Biochim Biophys Acta Mol Cell Res. 2021 Oct 6:119158. doi: 10.1016/j.bbamcr.2021.119158. Online ahead of print.

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.

PMID:34626680 | DOI:10.1016/j.bbamcr.2021.119158


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