Reduction in the Intestinal Epithelial Glutathione Redox Potential May Regulate Proliferation in the Neonatal Murine Gut

Abstract

The intracellular redox potential of the glutathione (GSH)/glutathione disulfide (GSSG) couple regulates many cellular processes. In vitro studies indicate that a reduced GSH/GSSG redox potential favors proliferation while an oxidized redox potential favors differentiation. Developmental regulation of intestinal growth and adaptation depends upon an appropriate balance between the two. However, how the ontogeny of intestinal epithelial cellular (IEC) GSH/GSSG redox regulates these processes in the developing intestine has not been characterized in vivo. IEC GSH/GSSG redox potential becomes increasingly reduced (primarily driven by a more than 4‐fold increase in IEC GSH concentration) over the first 3 weeks of life in all regions of the murine intestine with the biggest change occurring between 1 and 2 weeks. These changes are accompanied by an increase in intestinal growth and IEC proliferation as assessed by intestinal length, villus height/crypt depth, and Ki67 staining. Understanding how IEC GSH/GSSG redox potential is developmentally regulated may provide insight into how premature human intestinal redox states can be manipulated to optimize intestinal growth and adaptation.