Prostaglandin E2 accelerated recovery of chemotherapy-induced intestinal damage by increasing expression of cyclin D

Abstract

Intestinal stem cells (ISCs) play a crucial role in maintaining intestinal homeostasis upon chemotherapy and radiotherapy. It has been documented that prostaglandin E2 (PGE2) treatment improved hematopoietic stem cell function in vitro and in vivo, while the relationship between PGE2 and intestinal stem cells remains unclear. Presently, mice were exposed to PGE1, dmPGE2 and indomethacin. Numbers and function of ISCs were assessed by analyzing Olfm4+ ISCs. Intestinal protection of dmPGE2 was investigated on a 5-fluorouracil (5FU)-induced intestinal damage mouse model. The results showed that dmPGE2 treatment, but not PGE1, increased numbers of Olfm4+ ISCs in dose- and time-dependent manners. Indomethacin treatment decreased numbers of Olfm4+ ISCs. The beneficial effects of short-term dmPGE2 treatment on intestine were supported in a 5FU-induced intestinal damage model. Our data showed that 5FU treatment significantly decreased numbers of Olfm4+ ISCs and goblet cells in intestine, which could be ameliorated by dmPGE2 treatment. dmPGE2 treatment accelerated the recovery of 5FU-induced ISC injury via increasing expression of cyclin D1 and D2 in intestine. Furthermore, dmPGE2 treatment-induced expression of cyclin D1 and D2 might be mediated by up-regulation of FOXM1 expression in intestine. These findings feature PGE2 as an effective protector against chemotherapy-induced intestinal damage.