The protective effect of indoleamine 2, 3-dioxygenase 1 on the acute intestinal radiation injury
LAN Yanli1, 2, PI Wenhu2, MEI Dan1, YANG Haihua2, KONG Fengming1.
1.Key Laboratory of Radiation Oncology of Taizhou, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology,Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou 317000, China; 2.Department of Oncology,the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui 323000, China
LAN Yanli,PI Wenhu,MEI Dan, et al. The protective effect of indoleamine 2, 3-dioxygenase 1 on the acute intestinal radiation injury[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(4): 269-275,284.
Abstract：Objective: To investigate the protective mechanism of indoleamine 2, 3-dioxygenase 1 (IDO1) against radiation-induced acute intestinal injury. Methods: The expression level of IDO1 gene in colorectal cancer tissues and normal intestinal tissues were analyzed based on the TCGA and GTEX database. CRISPR/Cas9 technology was employed to delete the promoter and first exon sequences of IDO1 gene in IEC-6 cell for generating the IDO1 knockout (IDO1-/-, IDO1-KO) cell line, then wild type (WT) and knockout (IDO1-KO) IEC-6 cells were given radiation treatment. What’s more, C57BL/6 wild-type mice and IDO1 knockout (IDO1-/-) mice were given abdominal X-ray irradiation to establish radiation-induced intestinal damage model. Western blot was used to determine the IDO1 and epithelial tight junction proteins Claudin 1, Occludin, ZO-1 levels in cells and mouse intestinal tissues before and after radiation. Results: IDO1 gene was expressed in colon cancer, rectal cancer, and normal intestinal tissues. Compared with normal tissues, the expression level of IDO1 gene in cancer cells was higher, based on the TCGA and GTEX database analysis (P<0.05). Western blot indicated that IDO1 expressed in IEC-6 cells and mouse intestinal tissues in vitro and in vivo. The protein levels of IDO1, Claudin 1,
Occludin and ZO-1 showed significant changes after irradiation. The expression level of IDO1 increased significantly while tight junction protein Claudin 1, Occludin and ZO-1 decreased after radiation in IEC-6 cells and mouse intestinal tissues (P<0.05). Interestingly, the tight junction proteins decreased even more in IDO1-KO IEC-6 cells and mouse intestinal tissues (P<0.05). Conclusion: IDO1 has protective effect on intestinal radiation injury, which may be achieved by promoting the tight junctions of intestinal epithelial cells.
