(-)-Epigallocatechin-3-gallate promotes intestinal epithelial proliferation and barrier function after ischemia/reperfusion injury via activation of Nurr1

Abstract

Context (-)-Epigallocatechin-3-gallate (EGCG) is involved in cell proliferation and ischemia/reperfusion (I/R) injury of several organs. Objective To identify the role of EGCG in intestinal epithelial proliferation and barrier exposed to I/R injury. Material and methods Fifty Sprague-Dawley rats were divided into sham, I/R, I/R + EGCG (12.5 mg/kg), I/R + EGCG (25 mg/kg) and I/R + EGCG (50 mg/kg). I/R group rats were subjected to intestinal ischemia for 1 h and 6 h reperfusion. The rats were supplemented with EGCG 12.5, 25 and 50 mg/kg daily for 3 days via intraperitoneal injection before surgery. We used IEC-6 to expose to hypoxia/reoxygenation (H/R) injury to mimic I/R in vivo. IEC-6 cells were divided into control, H/R and H/R + EGCG (40 μmol/L). The effects of EGCG and its mechanism was explored. Results Pharmacological treatment with EGCG notably improves intestinal epithelial proliferation (12.5 mg/kg, 1.74-fold; 25 mg/kg, 2.93-fold, and 50 mg/kg, 4.33-fold) and barrier function after I/R injury. EGCG promoted cell proliferation (2.99-fold) and increased the expression of occludin (2.36-fold) and ZO-1 (1.64-fold) in IEC-6 cells after H/R injury. EGCG promoted proliferation of IEC-6 cells with ED50 values of 18.16 μmol/L. Further investigations indicated that EGCG activated Nurr1 expression in intestine after I/R injury. EGCG promote cell proliferation and increased the expression of occludin and ZO-1 in IEC-6 cells after H/R injury were abrogated in the knockdown of Nurr1 by siRNA. Discussion and conclusion Our findings indicate that EGCG promotes intestinal epithelial cell proliferation and barrier function after I/R injury in vitro and in vivo via activation of Nurr1.