Syndecan 1 is the predominant
heparan sulfate proteoglycan found on the surface of epithelial cells and, like
glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial
syndecan 1 would abrogate the gut-protective effects of enteral
glutamine. Both an in vitro and in vivo model of gut
ischemia-reperfusion (IR) was utilized. In vitro, intestinal epithelial cells underwent
hypoxia-reoxygenation to mimic gut IR with 2 mM (physiologic) or 10 mM
glutamine supplementation. Permeability,
caspase activity, cell growth, and cell surface and shed
syndecan 1 were assessed. In vivo, wild-type and
syndecan 1 knockout (KO) mice received ± enteral
glutamine followed by gut IR. Intestinal injury was assessed by
fluorescent dye clearance and histopathology, permeability as mucosal-to-serosal clearance ex vivo in everted sacs, and
inflammation by
myeloperoxidase (MPO) activity. In an in vitro model of gut IR,
glutamine supplementation reduced epithelial cell permeability and apoptosis and enhanced cell growth. Shed
syndecan 1 was reduced by
glutamine without an increase in
syndecan 1 mRNA. In vivo, intestinal permeability,
inflammation, and injury were increased after gut IR in wild-type mice and further increased in
syndecan 1 KO mice.
Glutamine's attenuation of IR-induced intestinal hyperpermeability,
inflammation, and injury was abolished in
syndecan 1 KO mice. These results suggest that
syndecan 1 plays a novel role in the protective effects of enteral
glutamine in the postischemic gut.