Involvement of DNA Damage Response via the Ccndbp1–Atm–Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis

Abstract

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.

Basics, Epidemiology, Diagnosis, and Management of Liver Tumor

“…These results suggested that Ccndbp1 contributed to activating the Atm–Chk2 pathway, in turn triggering inflammation and apoptosis of mucosal cells in the colon. (“Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis” by Horirome et al [ 6 ]). Based on this progress, it is essential to evaluate CCNDBP1 expression in the human liver samples of various chronic liver diseases that cause inflammation and fibrotic changes, and ultimately to apply these results to novel molecular therapy for the liver tumor.…”