Journal
JOURNAL OF CLINICAL MEDICINE
Volume 11, Issue 13, Pages -Publisher
MDPI
DOI: 10.3390/jcm11133674
Keywords
DSS; colitis; Ccndbp1; Atm; Chk2; DNA damage
Categories
Funding
- Japanese Society for the Promotion of Sciences [26293175]
- Ichiro Kanehara Foundation
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The DSS-induced colitis mouse model causes colon shortening and increased disease activity index, while also activating the Atm-Chk2 pathway and inducing cell apoptosis at the cellular level. Knockout mice lacking the Ccndbp1 gene exhibit better protection against DSS-induced colitis.
The dextran sodium sulfate (DSS)-induced colitis mouse model has been widely utilized for human colitis research. While its mechanism involves a response to double-strand deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (Atm)-checkpoint kinase 2 (Chk2) pathway activation related to such response remains unreported. Recently, we reported that cyclin D1-binding protein 1 (Ccndbp1) activates the pathway reflecting DNA damage in its knockout mice. Thus, this study aimed to examine the contribution of Ccndbp1 and the Atm-Chk2 pathway in DSS-induced colitis. We assessed the effect of DSS-induced colitis on colon length, disease activity index, and histological score and on the Atm-Chk2 pathway and the subsequent apoptosis in Ccndbp1-knockout mice. DSS-induced colitis showed distal colon-dominant Atm and Chk2 phosphorylation, increase in TdT-mediated dUTP-biotin nick end labeling and cleaved caspase 3-positive cells, and histological score increase, causing disease activity index elevation and colon length shortening. These changes were significantly ameliorated in Ccndbp1-knockout mice. In conclusion, Ccndbp1 contributed to Atm-Chk2 pathway activation in the DSS-induced colitis mouse model, causing inflammation and apoptosis of mucosal cells in the colon.
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