RESUMO
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.
