The in vivo-jetPEI-mediated SNIP1-DNA was injected intraperitoneally into colitis mice starting on day 4–9 after DSS exposure. The mice without receiving DSS treatment were also administrated intraperitoneally with SNIP1-DNA or control DNA as controls. A group of DSS exposed mice were injected intraperitoneally with in vivo-jetPEI mediated SNIP1-DNA (4 mg/ kg of body weight) starting on day 4–9.

Smad nuclear interacting protein 1 (SNIP1) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms involved are still largely unknown. Our results demonstrated that SNIP1 was markedly decreased in intestinal epithelial cells (IEC) from IBD patients compared with healthy controls. Impaired expression of SNIP1 caused a significant decrease of transepithelial electrical resistance but an increase of fluorescein isothiocyanate-dextran flux in Caco-2 monolayers, whereas overexpression of SNIP1 reversed such effects. Overexpression of SNIP1 also inhibited the activity of NF-kappaB p65 and proinflammatory cytokine production (e.g., TNF-alpha, IL-1beta, and IL-8) by IEC. Importantly, supplementation of exogenous SNIP1 significantly ameliorated intestinal mucosal inflammation in experimental colitis, characterized by less-severe intestinal epithelial barrier damage and decreased proinflammatory cytokine production. Our data thus demonstrated a novel mechanism whereby SNIP1 regulates intestinal inflammation through modulating intestinal epithelial barrier function. Targeting SNIP1 may provide a therapeutic approach for the treatment of IBD.