A protein is identified to save bowel inflammation patients

A group of researchers first demonstrated the role of stomach cancer-associated protein tyrosine phosphatase (SAP)-1 in the pathogenesis and prevention of Crohn's disease, ulcerative colitis, and other inflammatory bowel disorders. The group was led by Prof. MATOZAKI Takashi and Associate Prof. MURATA Yoji at the Kobe University Graduate School of Medicine Division of Molecular and Cellular Signaling
Inflammatory bowel diseases are disorders of unknown etiology that are often characterized by abdominal pain, diarrhea, bloody stool, fever, and weight loss. These diseases include Crohn's disease and ulcerative colitis. These symptoms effect too much on patients' daily life and the patients will be pushed at an elevated risk of mortality. And these patients are more likely to be linked with colorectal cancer.
A lot of studies published recently have demonstrated that intestinal epithelial cells are important in regulating bowel inflammation, but the underlying mechanism remains unknown. Before this, the scientists found that SAP-1 localizes to the microvilli of the brush border in gastrointestinal epithelial cells. The transmembrane-type tyrosine phosphatase SAP-1 has an extracellular domain that protrudes into the intestinal lumen and a cytoplasmic domain that mediates tyrosine dephosphorylation of proteins. They showed that SAP-1 ablation in a mouse model of inflammatory bowel disease resulted in a marked increase in the incidence and severity of bowel inflammation, which suggests that SAP-1 plays a protective role against colitis. What's more, carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific membrane protein, was identified as the target of SAP-1 tyrosine dephosphorylation. Suppression of CEACAM20 functions via dephosphorylation contributes to preventing colitis. They believe that their findings will drive the development of drugs that target SAP-1 and CEACAM20 to overcome intractable inflammatory bowel diseases by unlocking the anti-inflammatory mechanism of the intestinal epithelial cells.
The future researches of these scientists will be concentrated on taking advantage of the understanding of SAP-1 and CEACAM20 functions to develop new therapeutics for inflammatory bowel disease.
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