Enteric Glial Cell Network Function is Required for Epithelial Barrier Restitution following Intestinal Ischemic Injury in the Early Postnatal Period

Am J Physiol Gastrointest Liver Physiol. 2023 Dec 26. doi: 10.1152/ajpgi.00216.2022. Online ahead of print.ABSTRACTIschemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGC) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network density and glial activity were examined by gene set enrichment analysis, three-dimensional volume imaging and western blot and its function in regulating epithelial restitution assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate, and in vitro by co-culture assay. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete ...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research