Role of SIRT2 in intestinal barrier under cold exposure

Life Sci. 2023 Oct 1:330:121949. doi: 10.1016/j.lfs.2023.121949. Epub 2023 Jul 24.

Abstract

Prolonged cold exposure causes body stress and damages health. The intestinal environment is complex and variable, and direct contact with the external environment can easily cause stress, damage and even lead to diseases such as diarrhea.

Aims: This study aimed to reveal the role of cold exposure on ileum damage and the role of SIRT2 in this process.

Main methods: C57BL6 mice and SIRT2 knockout mice were used to construct a chronic cold exposure model (21 days, random 4 °C exposure for 3 h per day), which was tested by various methods, including intestinal permeability assays, morphological assays, ultrastructural assays, western blotting, and fluorescence staining. In vitro assays were performed on the mouse small intestinal epithelial cell line MODE-K to investigate the role of endoplasmic reticulum stress, SIRT2 knockout, and autophagy on tight junctions.

Key findings: The results showed that chronic cold exposure damaged the ileal epithelial barrier, with endoplasmic reticulum stress. Knockout of SIRT2 alleviates ileal injury via enhanced autophagy under cold exposure. And autophagy can restore the expression of ZO-1 under stress.

Significance: This study can provide potential target and basic data for the treatment of IBD and other disorders of the intestinal barrier. Autophagy may be an important means of restoring damage to the intestinal barrier.

Keywords: Autophagy; ER stress; FoxO1; Intestinal barrier; SIRT2; Tight junction.

MeSH terms

  • Animals
  • Intestinal Mucosa* / metabolism
  • Intestine, Small
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Permeability
  • Sirtuin 2* / genetics
  • Sirtuin 2* / metabolism
  • Tight Junctions / metabolism

Substances

  • Sirtuin 2
  • Sirt2 protein, mouse