Neonatal injury increases gut permeability by epigenetically suppressing E-cadherin in adulthood

Epithelial cell juntion integrity is thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD). Early life stressors are suspected to impact epithelial barrier function later in life. We postulated that based on our previous findings that early life exposure to an inflammatory event could lead to epigegenetic changes mediating an exagerated response to a second inflammatory insult as an adult. In addition, we hypothesized that this increased inflammatory response could be mediated by alterations in miRNA expression impacting essential junction protein E-cadherin. Rat neonates were divided randomly into four groups: 1) vehicle treatment in neontatal and adult stages (Ctl+Ctl); 2) vehicle treatment as neonates followed by inlammatory insult as adults (Ctl+AI); 3) neonatal inflammatory event and then sham treatment as adults (NI+Ctl); and 4) inflammatory insults both as neonates and adults (NI+AI). Trinitrobenzenesulfonic acid (TNBS) administered intraluminally into the colon served as inflammatory insult. Neonatal inflammation (NI) was induced on post-natal day 10 and adult inflammation (AI) was induced 6-8 weeks later. Seven days after the AI, rats were euthanilized. Colonic mucosa/submucosa was isolated, snap-frozen in liquid nitrogen, and pulverized. Total RNA was isolated using miRNeasy Mini Kit (Qiagen) and miRNA microarray was performed (LC Sciences).