期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1830, 期 3, 页码 2509-2516出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2012.11.007
关键词
Aryl hydrocarbon receptor; beta-Catenin; Cytochrome P-450 1A1; E-cadherin; E-cadherin carboxy terminal fragment 2; S-MEM
资金
- Ministry of Education, Culture, Sports, Science and Technology (Monbu Kagakusho) [21510065]
- Global Environment Research Fund of the Ministry of the Environment, Japan [C-0803]
- Grants-in-Aid for Scientific Research [21510065] Funding Source: KAKEN
Background: The aryl hydrocarbon (Ah) receptor is one of the best known ligand-activated transcription factors. The present study has focused on the wound-healing process on Ah receptor function. Methods: Depletion of calcium from culture medium of Caco-2 human colon carcinoma cells by transfer to Minimal Essential Medium (Spinner Modification; S-MEM) destroyed adherens junctions and the cells were used as the model of wound-healing process. Results: Calcium depletion induced both nuclear translocation of the Ah receptor, and increased expression of CYP1A1 and Slug mRNAs in Caco-2 cells. However, expression of Slug mRNA was not significantly induced by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Knockdown of the Ah receptor and treatment with Ah receptor antagonists decreased level of CYP1A1 mRNA. The fragment of E-cadherin released by gamma-secretase was not involved in induction of CYP1A1 mRNA following S-MEM treatment. Knockdown of beta-catenin increased levels of Ah receptor mRNA, which may be attributable to direct or indirect involvement of beta-catenin in suppression of the Ah receptor gene. Conclusions: Our results suggest that mRNA induction of some genes by destruction of adherens junctions depends on the Ah receptor. beta-Catenin, one of the components of the adherens junction, was released from the E-cadherin complex, which resulted in its increased interaction with the Ah receptor, and was translocated into the nucleus, and consequently the target genes would be transcribed. General significance: Our observations suggest that some aspects of the molecular mechanism of wound healing involve the Ah receptor. (C) 2012 Elsevier B.V. All rights reserved.
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