L-type amino acid transporter 1 deficiency delays intestinal tissue repair in dextran sulfate sodium-induced colitis.

BACKGROUND

Inflammatory bowel disease (IBD) remains a public health concern, with increasing incidence and prevalence globally. L-type amino acid transporter 1 (LAT1) has been reported to be upregulated during the active phase of ulcerative colitis; however, its role in the course of colitis remains unclear. In this study, we aimed to explore the role of LAT1 in colitis.

METHODS

Mice with intestinal epithelium-specific deletions of LAT1 (LAT1fl/fl; vil-cre) were treated with dextran sulfate sodium (DSS) to investigate its role in colitis. Organoids derived from these mice were also analyzed.

RESULTS

LAT1 expression was significantly upregulated in DSS-induced colitis. LAT1fl/fl; vil-cre mice did not show increased susceptibility during DSS-induced colitis but exhibited more severe injury following DSS treatment. Its deficiency did not significantly influence inflammatory cytokine gene expression and epithelial proliferation or apoptosis. However, during the tissue repair phase, LAT1fl/fl; vil-cre mice showed a reduced number of colonic crypts and Hes-1 gene expression. Accordingly, organoids derived from LAT1-deficient crypts exhibited a markedly reduced capacity for colonic organoid formation.

CONCLUSIONS

LAT1 deficiency in the intestinal epithelium delays tissue repair by impairing colonic crypt regeneration. Our findings offer insights into how nutrient availability in the tissue environment is sensed by cells and may influence the control of colonic tissue recovery from inflammatory damage.