Endogenous prion protein attenuates experimentally induced colitis

Area of Science:

• Gastroenterology
• Neuroimmunology
• Molecular Biology

Background:

• The cellular prion protein (PrP(C)) is present in the gut's nervous system and lamina propria.
• The specific roles of PrP(C) in gastrointestinal function and inflammation remain largely uncharacterized.
• PrP(C) is known to have cytoprotective properties against various physiological stressors.

Purpose of the Study:

• To investigate the hypothesis that PrP(C) expression levels influence the severity of experimental colitis.
• To elucidate the protective or detrimental effects of PrP(C) in a murine model of inflammatory bowel disease.

Main Methods:

• Dextran sodium sulfate (DSS)-induced colitis was established in wild-type, PrP(C)-overexpressing (Tga20), and PrP(C)-deficient (Prnp(-/-)) mice.
• Colon length, disease severity scores, and histological activity were assessed on day 7.
• Expression and phosphorylation levels of pro-survival and pro-inflammatory molecules were analyzed.

Main Results:

• PrP(C)-overexpressing Tga20 mice were resistant to DSS-induced colitis, showing minimal weight loss, colon shortening, and milder histopathology.
• Prnp(-/-) mice exhibited exacerbated colitis symptoms compared to wild-type controls.
• DSS treatment upregulated PrP(C) expression in the colon, and Tga20 mice displayed elevated pro-survival signaling and reduced pro-inflammatory markers.

Conclusions:

• PrP(C) possesses a significant cytoprotective and anti-inflammatory function in the murine colon.
• Modulating PrP(C) levels may represent a therapeutic strategy for inflammatory bowel diseases like colitis.