| Autor: |
Sasaki T; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Fujiwara-Tani R; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Luo Y; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Ogata R; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Sasaki R; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Ikemoto A; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Nishiguchi Y; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Nakashima C; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Kishi S; Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan., Fujii K; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Ohmori H; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan., Oue N; Pathology Laboratory, Miyoshi Central Hospital, 10531 Higashi-Sakaya, Miyoshi 728-8502, Hiroshima, Japan., Kuniyasu H; Department of Molecular Pathology, Nara Medical University, 840 Shijo-Cho, Kashihara 634-8521, Nara, Japan. |
| Abstrakt: |
Abnormalities in mucosal immunity are involved in the onset and progression of ulcerative colitis (UC), resulting in a high incidence of colorectal cancer (CRC). While high-mobility group box-1 (HMGB1) is overexpressed during colorectal carcinogenesis, its role in UC-related carcinogenesis remains unclear. In the present study, we investigated the role of HMGB1 in UC-related carcinogenesis and sporadic CRC. Both the azoxymethane colon carcinogenesis and dextran sulfate sodium colitis carcinogenesis models demonstrated temporal increases in mucosal HMGB1 levels. Activated CD8+ cells initially increased and then decreased, whereas exhausted CD8+ cells increased. Additionally, we observed increased regulatory CD8+ cells, decreased naïve CD8+ cells, and decreased mucosal epithelial differentiation. In the in vitro study, HMGB1 induced energy reprogramming from oxidative phosphorylation to glycolysis in CD8+ cells and intestinal epithelial cells. Furthermore, in UC dysplasia, UC-related CRC, and hyperplastic mucosa surrounding human sporadic CRC, we found increased mucosal HMGB1, decreased activated CD8+ cells, and suppressed mucosal epithelial differentiation. However, we observed increased activated CD8+ cells in active UC mucosa. These findings indicate that HMGB1 plays an important role in modulating mucosal immunity and epithelial dedifferentiation in both UC-related carcinogenesis and sporadic CRC. |
