Related Experiment Video
Updated: May 20, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Breakdown of mucin as barrier to digestive enzymes in the ischemic rat small intestine
Marisol Chang1, Tom Alsaigh, Erik B Kistler
1Department of Bioengineering, University of California San Diego La Jolla, California, United States of America.
Abstract:
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.
Insights
Intestinal ischemia disrupts mucin, a key protein in the gut barrier, increasing permeability. Mucin protects the epithelial barrier from digestive enzymes, which actively damage cells when the mucin layer is compromised.
Area of Science:
- Gastroenterology
- Epithelial Biology
- Mucosal Immunology
Background:
- The intestinal epithelial barrier's integrity is crucial for gastrointestinal health.
- Mucin, the primary component of the mucus layer, is vital for barrier function.
- Intestinal ischemia can disrupt the mucosal barrier, leading to pathology.
Purpose of the Study:
- To investigate the role of mucin in protecting the intestinal epithelial barrier.
- To determine if mucin breakdown precedes or follows epithelial damage during ischemia.
- To assess the contribution of digestive enzymes to mucin degradation and epithelial injury.
Main Methods:
- A rat model of splanchnic arterial occlusion (SAO) was employed.
- Degradation of mucin 2, mucin 13, E-cadherin, and toll-like receptor 4 (TLR4) was analyzed.
- In vitro experiments assessed mucin's protective effect against trypsin-mediated damage.
Main Results:
- Splanchnic arterial occlusion (SAO) led to mucin 2 degradation and mucin 13 fragmentation.
- Protease inhibition did not prevent mucin degradation following SAO.
- Epithelial barrier disruption, increased intestinal permeability, and degradation of E-cadherin and TLR4 were observed.
- In vitro, mucin protected epithelial cells from trypsin-induced damage and reduced permeability.
Conclusions:
- Mucin is essential for maintaining the integrity of the intestinal mucosal barrier.
- Ischemia, not digestive enzymes, initially disrupts mucin integrity.
- Digestive enzymes actively contribute to epithelial cell damage when the mucin barrier is compromised.
Related Concept Videos
01:25Mucosal Barrier of the Stomach
Within parietal cells, carbonic acid is first formed through the reaction of water and carbon dioxide. The dissociation of carbonic acid releases bicarbonate and hydrogen ions. The bicarbonate...
01:24Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors
01:24Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
01:30Mechanical and Chemical Digestion in the Small Intestine
Mechanical digestion in the small intestine involves movements such as segmentations and migrating motility complexes (MMCs), primarily controlled by the myenteric plexus. Segmentations are localized contractions occurring in areas of the intestine distended by chyme—a mixture of partially digested food. These contractions mix chyme with digestive juices, facilitating absorption...
01:27Histology of the Small Intestine
The intestinal lining features transverse folds called circular folds, each housing fingerlike projections known as intestinal villi. These villi are covered by a layer of simple columnar epithelium, also referred to as...
01:29Intestinal Phase of Digestion
The arrival of the chyme in the small intestine distends the duodenum, which triggers the enterogastric reflex. This distension...