Activating Transcription Factor 3 Protects against Restraint Stress-Induced Gastrointestinal Injury in Mice

Abstract

Psychological stress increases the risk of gastrointestinal (GI) tract diseases, which involve bidirectional communication of the GI and nerves systems. Acute stress leads to GI ulcers; however, the mechanism of the native cellular protection pathway, which safeguards tissue integrality and maintains GI homeostasis, remains to be investigated. In a mouse model of this study, restraint stress induced GI leakage, abnormal tight junction protein expression, and cell death of gut epithelial cells. The expression of activating transcription factor 3 (ATF3), a stress-responsive transcription factor, is upregulated in the GI tissues of stressed animals. ATF3-deficient mice displayed an exacerbated phenotype of GI injuries. These results suggested that, in response to stress, ATF3 is part of the native cellular protective pathway in the GI system, which could be a molecular target for managing psychological stress-induced GI tract diseases.

P-Selectin is a Critical Factor for Platelet-Mediated Protection on Restraint Stress-Induced Gastrointestinal Injury in Mice

“…P-selectin gene knockout (KO) ( Selp −/ − ) mice were employed to specify the involvement of P-selectin regulation under stress. Using the restraint stress mouse model orally fed with Evans blue dye [ 15 ], we found that Selp −/ − mice displayed higher GI leakage than the wild -type mice ( Figure 2 ), implicating the protective role of P-selectin in the GI system. Because male ( Figure 2 ) and female ( Figure S3 ) mice behaved similarly in response to the stress, this suggested that there are no sex differences in stress-induced GI leakage in mice.…”

“…Pathophysiological changes associated with anxiety and stressed behavior of experimental animals could occur after restraint stress [ 12 ]. Evans blue, a GI-nonabsorbable dye, will not normally appear in plasma when orally fed [ 15 ]. By examining the plasma levels of Evans blue, we can measure stress-induced GI leakage in real time [ 15 ].…”

“…Evans blue, a GI-nonabsorbable dye, will not normally appear in plasma when orally fed [ 15 ]. By examining the plasma levels of Evans blue, we can measure stress-induced GI leakage in real time [ 15 ]. In our previous study that used Evans blue and restraint stress mouse model, acute restraint stress leads to GI leakage, which is associated with the death of gut epithelial cells [ 15 ].…”

“…By examining the plasma levels of Evans blue, we can measure stress-induced GI leakage in real time [ 15 ]. In our previous study that used Evans blue and restraint stress mouse model, acute restraint stress leads to GI leakage, which is associated with the death of gut epithelial cells [ 15 ]. However, the detailed mechanism remains unclear.…”

Nanodiamond-Induced Thrombocytopenia in Mice Involve P-Selectin-Dependent Nlrp3 Inflammasome-Mediated Platelet Aggregation, Pyroptosis and Apoptosis

“…To distinguish populations of platelets, NDs and platelet-ND aggregates, CellTracker Blue Dye (ThermoFisher Scientific) labeled mouse platelets, and red fluorescent 50 nm NDs (brFND-50, FND Biotech) were used in this experiment. The counts of platelet aggregates per field (> 400 pixels) and the total platelet aggregate area (pixels) per field were analyzed using ImageJ software (version 1.32; National Institutes of Health, USA) ( 38 , 68 ).…”