Weaning-induced cell cycle arrest through up-regulation of p21 and p27 in the jejunum of piglets

Abstract

This study was aimed at investigating the effects of weaning on jejunal redox status, morphology and expression of cell cycle regulators in piglets. A total of 120 new-born piglets from 12 litters were divided into two groups: the control (suckled normally) and weaning group (weaned at day 21). Six piglets from each group were slaughtered at day 22, day 25 and day 28. Results showed that weaning increased the serum hydrogen peroxide (H₂O₂ ) and malondialdehyde (MDA), decreased inhibitory hydroxyl radical (IHR) concentrations and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities at day 25. Furthermore, the jejunal nitric oxide (NO) level was increased at days 22 and 28, while H₂O₂ concentration was increased at days 22, 25 and 28. Results of jejunum morphology showed weaning decreased villous height and width, and increased crypt depth at day 25. Relative mRNA and protein expression showed that Smad4 was decreased at day 25 and then increased at day 28. The expression of p21 and p27 were significantly increased by weaning at days 25 and 28, but cyclin D and cyclin E showed no significant differences compared with control group. In conclusion, weaning increased the serum and jejunal reactive oxygen species (ROS) production, inhibited jejunum development and cell cycle progression through down-regulation of Smad4 and up-regulation of p21 and p27 of piglets, which further explained weaning-induced stress syndrome.

Keywords: Proliferation, intestine, reactive oxygen species, weaning