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: Gene expression analysis showed that DSS induced a significant increase in the expression of inflammatory cytokines and chemokines in WT mice treated with DSS over water-treated mice, which was further increased in UNC5B−/+ mice treated with DSS (Fig. 5). Increased inflammation was associated with increased apoptosis in the colonic epithelial cells which was further increased in UNC5B−/+ mice treated with DSS (Fig. 6A). Consistent with increased apoptosis, the expression of several pro-apoptotic genes was significantly increased in UNC5B+/+ WT mice treated with DSS as compared to water-treated control, which was further increased in UNC5B+/− mice treated with DSS (Fig. 6B).
Affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, USA.