Abstract
Mechanical barriers play a key role in maintaining the normal function of the intestinal mucosa. The barrier function of intestinal epithelial cells is significantly damaged after severe hypoxia. However, the molecular mechanisms underlying this hypoxia-induced damage are still not completely clear. Through the establishment of an in vitro cultured intestinal epithelial cell monolayer model (Caco-2), we treated cells with hypoxia or drugs [jasplakinolide or latrunculin A (LatA)] to detect changes in the transepithelial electrical resistance (TER), the expression of the cellular tight junction (TJ) proteins zonula occludens-1 (ZO-1) and occludin, the distribution of F-actin, the ratio of F-actin/G-actin content, and the expression of the cofilin protein. The results showed that hypoxia and drug treatment could both induce a significant reduction in the TER of the intestinal epithelial cell monolayer and a significant reduction in the expression of the ZO-1 and occludin protein. Hypoxia and LatA could cause a significant reduction in the ratio of F-actin/G-actin content, whereas jasplakinolide caused a significant increase in the ratio of F-actin/G-actin content. After hypoxia, cofilin phosphorylation was decreased. We concluded that the barrier function of the intestinal epithelial cell monolayer was significantly damaged after severe burn injury. The molecular mechanism might be that hypoxia-induced F-actin depolymerization and an imbalance between F-actin and G-actin through cofilin activation resulted in reduced expression and a change in the distribution of cellular TJ proteins.
Highlights
The intestine has always been considered the main organ impacted by surgical stress, such as trauma from severe burns
We further explored the effect of hypoxia on the distribution of the tight junction (TJ) proteins zonula occludens-1 (ZO-1) and occludin using immunofluorescence combined with confocal microscopy
Damage to the intestinal barrier function is an important cause of bacterial translocation, inflammatory responses, sepsis, multiple organ dysfunction, high metabolic responses, and even death after severe burn injury (Carter et al, 2013; Feng et al, 2019)
Summary
The intestine has always been considered the main organ impacted by surgical stress, such as trauma from severe burns. Damage to the barrier function of the intestine is an important factor in pathophysiological disorders of the body after severe burn injury (Osuka et al, 2017; He et al, 2019). Cell retraction is an important link between barrier function damage and increased permeability in intestinal epithelial cells. It is both regulated by myosin and influenced by actin. F-actin and G-actin maintain a dynamic balance When this balance is broken, the barrier function is damaged (Turner, 2009). It has been shown that severe burn injury causes TJ damage in intestinal epithelial cells and reduces intestinal barrier functions.
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