Open Access

Aryl hydrocarbon receptor activation maintained the intestinal epithelial barrier function through Notch1 dependent signaling pathway

  • Authors:
    • Zhongze Liu
    • Liangzi Li
    • Weigang Chen
    • Qimeng Wang
    • Weidong Xiao
    • Yuanhang Ma
    • Baifa Sheng
    • Xiang Li
    • Lihua Sun
    • Min Yu
    • Hua Yang
  • View Affiliations

  • Published online on: December 22, 2017     https://doi.org/10.3892/ijmm.2017.3341
  • Pages: 1560-1572
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intestinal ischemia/reperfusion (I/R) induces disruption of the intestinal barrier function. Aryl hydrocarbon receptor (AhR) has a vital role in maintaining the intestinal barrier function. However, the precise mechanism by which AhR maintains intestinal barrier function remains unclear. Notch1 signaling is downstream of AhR, and has also been reported to have a role in the development of tight junctions (TJs) and maintenance of intestinal homeostasis. Therefore, we hypothesized that AhR activation may attenuate the intestinal barrier dysfunction through increased activation of Notch1 signaling. Adult C57BL/6J mice were divided into three groups: Sham, I/R and I/R + 6-formylindolo(3,2-b)carbazole (Ficz) groups. Mice were sacrificed after I/R for 6 h and the intestine was harvested for histological examination, mRNA and protein content analysis, and mucosal permeability investigation. Additionally, a hypoxic Caco‑2 cell culture model was used to evaluate the role of AhR‑Notch1 signaling in the development of TJs and epithelial permeability in vitro. The AhR‑Notch1 signaling components and TJ proteins were assessed by reverse transcription‑quantitative polymerase chain reaction, western blotting, immunohistochemistry or immunofluorescence staining. Epithelial permeability was detected by transepithelium electrical resistance. The data demonstrated that Ficz significantly attenuated the intestinal tissue damage and the disrupted distribution of TJs, increased the expression of TJ proteins, reversed the decrease in TER and upregulated epithelial Notch1 signaling following intestinal I/R in vivo and hypoxia in vitro. Furthermore, inhibition of Notch1 signaling by N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (inhibitor of Notch signaling) counteracted the effects of Ficz on the development of TJs in hypoxic Caco‑2 cells. In conclusion, AhR activation ameliorated epithelial barrier dysfunction following intestinal I/R and hypoxia through upregulation of Notch1 signaling, which suggests that AhR may be a potential pharmaceutical agent to combat this condition.
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March 2018
Volume 41 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Liu, Z., Li, L., Chen, W., Wang, Q., Xiao, W., Ma, Y. ... Yang, H. (2018). Aryl hydrocarbon receptor activation maintained the intestinal epithelial barrier function through Notch1 dependent signaling pathway. International Journal of Molecular Medicine, 41, 1560-1572. https://doi.org/10.3892/ijmm.2017.3341
MLA
Liu, Z., Li, L., Chen, W., Wang, Q., Xiao, W., Ma, Y., Sheng, B., Li, X., Sun, L., Yu, M., Yang, H."Aryl hydrocarbon receptor activation maintained the intestinal epithelial barrier function through Notch1 dependent signaling pathway". International Journal of Molecular Medicine 41.3 (2018): 1560-1572.
Chicago
Liu, Z., Li, L., Chen, W., Wang, Q., Xiao, W., Ma, Y., Sheng, B., Li, X., Sun, L., Yu, M., Yang, H."Aryl hydrocarbon receptor activation maintained the intestinal epithelial barrier function through Notch1 dependent signaling pathway". International Journal of Molecular Medicine 41, no. 3 (2018): 1560-1572. https://doi.org/10.3892/ijmm.2017.3341