UNC5B receptor deletion exacerbates DSS-induced colitis in mice by increasing epithelial cell apoptosis.
Bottom Line: Overexpression of UNC5B human colon epithelial cells suppressed DSS-induced apoptosis and caspase-3 activity.Moreover, DSS induced large amount of netrin-1 and shRNA mediated knockdown of netrin-1 induction exacerbated DSS-induced epithelial cell apoptosis.Our results suggest that UNC5B is a critical mediator of cell survival in response to stress in colon.
Affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, USA.Show MeSH
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Mentions: To determine whether UNC5B has the protective role in other models of tissue injury, we treated WT and heterozygous knockout mice with DSS as described in Methods. Body weight was monitored. Wild-type mice developed colitis as seen by a significant reduction in bw on Day 5 and reached the maximum of Day 9 when we killed. However, UNC5B−/+ mice developed much severe colitis as seen by significant loss of bw, increase in colon weight and reduction in colon length (Fig. 2A–D). Consistent with changes in bw and colon weight, histological examination shows severe tissue injury (Fig. 3A–D) and leucocyte infiltration (Fig. 4A and B and Fig. S2) in WT, which was further increased in UNC5B−/+ mice colon.
Affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, USA.