Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating hnRNPA1/Gprc5a signaling

Abstract Intestinal ischemia/reperfusion (I/R) injury is a severe clinical condition lacking diagnostic markers and has poorly understood molecular mechanisms. Although plasma exosomal circular RNAs (circRNAs) are valuable biomarkers and therapeutic targets for various diseases, their role in intestinal I/R injury remains unknown. This study screens the expression profile of circRNAs in intestinal tissue exosomes collected from intestinal I/R mice and identified circEZH2_005 as a significantly downregulated exosomal circRNA in the plasma of clinical cardiac surgery patients who developed postoperative intestinal I/R injury. The expression of plasma exosomal circEZH2_005 was negatively correlated with the intestinal injury grade. Notably, exosomal circEZH2_005 displayed a significant diagnostic value for intestinal injury induced by I/R. Mechanistically, circEZH2_005 was highly expressed in intestinal crypt cells. CircEZH2_005 upregulation significantly promoted the proliferation of Lgr5+ stem cells by direct interaction with hnRNPA1 and enhanced Gprc5a stability, thereby alleviating I/R-induced intestinal mucosal damage. Hence, exosomal circEZH2_005 may help intestinal I/R injury diagnosis and treatment.