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Chronic Dexamethasone Exposure Induced Mucosal Injuries by Activating Epithelial Apoptosis and Inflammatory Response in The Colon of Goats
Author(s) -
Cai Liuping
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.703.6
Subject(s) - endocrinology , apoptosis , chronic stress , downregulation and upregulation , glucocorticoid receptor , medicine , nitric oxide synthase , tlr4 , cyclin dependent kinase , glucocorticoid , biology , chemistry , inflammation , nitric oxide , cell cycle , biochemistry , gene
Background Chronic stress has a profound effect on health in both animals and humans. Chronic stress can influence the level of glucocorticoid. Dexamethasone (Dex), a synthetic glucocorticoid, is used to induce chronic stress. However, the aim of the present study was to investigate the effect of chronic stress caused by long term injection of Dex on changes on colonic epithelium in goats. Results The results show that chronic stress increased the number of TUNEL‐apoptosis‐positive cells, upregulated caspase‐3 enzyme activity, and decreased the proteins expression of cell proliferation markers proliferating cell nuclear antigen (PCNA) and Cyclin D2 (CCND2) in the colonic epithelium. The gene expression of claudin‐1, claudin‐4 and ZO‐1 were upregulated by Dex (P < 0.05). But claudin‐4 protein expression was increased by Dex (P < 0.05). The gene expression of cell cycle such as CDKs (cyclin‐dependent kinases), CCND1, and CCND2 were all increased by Dex (P < 0.05). The gene expression of inflammtory cytokines interlukin‐10 (IL‐10), interlukin‐1β (IL‐1β), inducible nitric oxide synthase 2 (iNOS2), and inflammatory‐related transcriptional factors mitogen‐activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NFκB) were all upregulated by Dex (P < 0.05). The protein expression of NFκB and Toll‐like receptors (TLR4) were increased by Dex (P < 0.05). Moreover, the results showed that the methylation levels of total DNA and TLR4, caspase‐3 promoter were significantly decreased in the colonic epithelium compared to control group. Conclusions These results indicated that long‐term injection of a low dosage of Dex caused damage to the colon epithelium and inhibition of cell proliferation, and result in the activation of the inflammatory response and decreased methylation of the total DNA. Support or Funding Information 1. National Nature Science Foundation of China (project no.31572433) 2. The Program for New Century Excellent Talents in University (NCET‐13‐0862) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .