Severe Burn-Induced Intestinal Epithelial Barrier Dysfunction Is Associated With Endoplasmic Reticulum Stress and Autophagy in Mice.

Yalan Huang,Fengjun Wang,Yu Wang,Hui Ren,Pei Wang,Yanhai Feng

doi:10.3389/fphys.2018.00441

Yalan Huang, Fengjun Wang + Show 4 more

Open Access

https://doi.org/10.3389/fphys.2018.00441

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Abstract

The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction. Mice received a 30% total body surface area (TBSA) full-thickness burn, and were sacrificed at 0, 1, 2, 6, 12 and 24 h postburn. The results showed that intestinal permeability was increased significantly after burn injury, accompanied by the damage of mucosa and the alteration of TJ proteins. Severe burn induced ER stress, as indicated by increased intraluminal chaperone binding protein (BIP), CCAAT/enhancer-binding protein homologous protein (CHOP) and inositol-requiring enzyme 1(IRE1)/X-box binding protein 1 splicing (XBP1). Autophagy was activated after burn injury, as evidenced by the increase of autophagy related protein 5 (ATG5), Beclin 1 and LC3II/LC3I ratio and the decrease of p62. Besides, the number of autophagosomes was also increased after burn injury. The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier.

Highlights

The intestinal epithelia form a critical interface between the intestinal mucosa and the luminal environment, providing a barrier against luminal toxins, pathogenic organisms and antigenic molecules
Having found the increase of intestinal permeability following severe burn injury, we investigated the expression of intestinal epithelial tight junction (TJ) proteins in severely burned mice
It is suggested that the changes of TJ proteins in intestinal epithelia are involved in the intestinal epithelial barrier dysfunction following severe burn

Summary

Introduction

The intestinal epithelia form a critical interface between the intestinal mucosa and the luminal environment, providing a barrier against luminal toxins, pathogenic organisms and antigenic molecules. Many investigators, including ourselves, have found that severe burn injury directly induces the intestinal TJ barrier dysfunction in both patients and animals, resulting in the increased intestinal permeability, bacterial translocation, systemic inflammatory response syndrome, hypercatabolism, sepsis, and multiple organ dysfunction syndrome (Magnotti and Deitch, 2005; Arrieta et al, 2009; Chen et al, 2012; Carter et al, 2013; Clark et al, 2017). The mechanisms of intestinal epithelial barrier dysfunction induced by severe burn injury still remain unclear. In order to clinically improve recovery and survival of severe burn victims, it is imperative to get a better understanding of the mechanisms that mediate the intestinal epithelial barrier dysfunction following severe burn injury

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