Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

• DOI: 10.3389/fphys.2022.896951
• Publication Date: 2022-08-19T06:03:01Z
• Authors: Isabel A. Jimenez; Allison P. Stilin; Kanako Morohaku; Mahmoud H. Hussein; Prasanthi P. Koganti; Vimal Selvaraj
• Keywords: Translocator protein; CD36

In human patients and animal models of ulcerative colitis (UC), upregulation the mitochondrial translocator protein (TSPO) in colon is consistent with inflammation. Although molecular function for TSPO remains unclear, it has been investigated as a therapeutic target ameliorating UC pathology. this study, we examined susceptibility Tspo gene-deleted (Tspo-/- ) mice to insults provided by dextran sodium sulfate (DSS)-induced acute model. Our results show that clinical signs pathology were severely exacerbated Tspo-/- compared control Tspofl/fl cohorts. Histopathology showed extensive inflammation epithelial loss caused an aggravated disease. Colonic gene expression uncovered etiology linked precipitous integrity disproportionate mast cell activation assessed tryptase levels colons. Evaluation baseline homeostatic shifts colons revealed changes noted elevated Cdx2, Cd36 Mcp6, general indicators lower proliferation capacity fatty acid oxidation. These findings demonstrate intact physiological serves limit UC, provide systemic basis investigating TSPO-targeting mechanistic therapeutics.