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

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 12; p. 3530
• Main Authors: Chuang, Dun-Jie, Pethaperumal, Subhashree, Siwakoti, Bijaya, Chien, Hung-Jen, Cheng, Ching-Feng, Hung, Shih-Che, Lien, Te-Sheng, Sun, Der-Shan, Chang, Hsin-Hou
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.12.2021; MDPI
• Subjects: Activating transcription factor 3; Activating Transcription Factor 3 - deficiency; Activating Transcription Factor 3 - metabolism; Animals; Antibodies; ATF3; Caspase 3 - metabolism; Cell death; Chromatography; Duodenum - drug effects; Duodenum - metabolism; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Flow cytometry; Gastrointestinal Diseases - blood; Gastrointestinal Diseases - etiology; Gastrointestinal tract; Gene expression; Gene Expression Regulation; gut epithelial cell; Homeostasis; intestinal leakage; Laboratory animals; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerves; Phenotypes; Proton Pump Inhibitors - pharmacology; Restraint, Physical; RNA, Messenger - genetics; RNA, Messenger - metabolism; Small intestine; Stomach; Stress, Psychological - blood; Stress, Psychological - complications; tight junction; Tight Junction Proteins - genetics; Tight Junction Proteins - metabolism; Transcription factors; Ulcers; United States > US; Taiwan; gastrointestinal tract; cell death; gut epithelial cell; intestinal leakage; stress ulcer; ATF3; tight junction
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10123530

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.