RGD Reference Report - Breakdown of mucin as barrier to digestive enzymes in the ischemic rat small intestine. - Rat Genome Database

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Breakdown of mucin as barrier to digestive enzymes in the ischemic rat small intestine.

Authors: Chang, M  Alsaigh, T  Kistler, EB  Schmid-Schonbein, GW 
Citation: Chang M, etal., PLoS One. 2012;7(6):e40087. doi: 10.1371/journal.pone.0040087. Epub 2012 Jun 29.
RGD ID: 7349363
Pubmed: PMID:22768227   (View Abstract at PubMed)
PMCID: PMC3387149   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0040087   (Journal Full-text)

Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal ischemia. This event is accompanied by entry of pancreatic digestive enzymes into the intestinal wall. We hypothesize that the mucin-containing mucus layer is the main barrier preventing digestive enzymes from contacting the epithelium. Mucin breakdown may render the epithelium accessible to pancreatic enzymes, causing its disruption and increased permeability. The objective of this study was to investigate the role of mucin as a protection for epithelial integrity and function. A rat model of 30 min splanchnic arterial occlusion (SAO) was used to study the degradation of two mucin isoforms (mucin 2 and 13) and two epithelial membrane proteins (E-cadherin and toll-like receptor 4, TLR4). In addition, the role of digestive enzymes in mucin breakdown was assessed in this model by luminal inhibition with acarbose, tranexamic acid, or nafamostat mesilate. Furthermore, the protective effect of the mucin layer against trypsin-mediated disruption of the intestinal epithelium was studied in vitro. Rats after SAO showed degradation of mucin 2 and fragmentation of mucin 13, which was not prevented by protease inhibition. Mucin breakdown was accompanied by increased intestinal permeability to FITC-dextran as well as degradation of E-cadherin and TLR4. Addition of mucin to intestinal epithelial cells in vitro protected against trypsin-mediated degradation of E-cadherin and TLR4 and reduced permeability of FITC-dextran across the monolayer. These results indicate that mucin plays an important role in the preservation of the mucosal barrier and that ischemia but not digestive enzymes disturbs mucin integrity, while digestive enzymes actively mediate epithelial cell disruption.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MUC13Humanischemia  ISOMuc13 (Rattus norvegicus)protein:increased degradation:jejunumRGD 
MUC2Humanischemia  ISOMuc2 (Rattus norvegicus)protein:decreased expression:jejunumRGD 
Muc13Ratischemia  IEP protein:increased degradation:jejunumRGD 
Muc13Mouseischemia  ISOMuc13 (Rattus norvegicus)protein:increased degradation:jejunumRGD 
Muc2Ratischemia  IEP protein:decreased expression:jejunumRGD 
Muc2Mouseischemia  ISOMuc2 (Rattus norvegicus)protein:decreased expression:jejunumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Muc13  (mucin 13, cell surface associated)
Muc2  (mucin 2, oligomeric mucus/gel-forming)

Genes (Mus musculus)
Muc13  (mucin 13, epithelial transmembrane)
Muc2  (mucin 2)

Genes (Homo sapiens)
MUC13  (mucin 13, cell surface associated)
MUC2  (mucin 2, oligomeric mucus/gel-forming)


Additional Information