論文

査読有り 国際誌
2019年10月15日

Aryl Hydrocarbon Receptor Directly Regulates Artemin Gene Expression.

Molecular and cellular biology
  • Tomohiro Edamitsu
  • ,
  • Keiko Taguchi
  • ,
  • Eri H Kobayashi
  • ,
  • Ryuhei Okuyama
  • ,
  • Masayuki Yamamoto

39
20
記述言語
英語
掲載種別
DOI
10.1128/MCB.00190-19

Transgenic mice expressing a constitutively active form of the aryl hydrocarbon receptor in keratinocytes (AhR-CA mice) develop severe dermatitis that substantially recapitulates the pathology of human atopic dermatitis. The neurotrophic factor artemin (Artn) is highly expressed in the epidermis of AhR-CA mice and causes hypersensitivity to itch (alloknesis) by elongating nerves into the epidermis. However, whether the Artn gene is regulated directly by AhR or indirectly through complex regulation associated with AhR remains unclear. To this end, we previously conducted chromatin immunoprecipitation-sequencing analyses of the Artn locus and found a xenobiotic response element (XRE) motif located far upstream (52 kb) of the gene. Therefore, in this study, we addressed whether the XRE actually regulates the Artn gene expression by deleting the region containing the motif. We generated two lines of ArtnΔXRE mice. In the mouse epidermis, inducible expression of the Artn gene by the AhR agonist 3-methylcholanthrene was substantially suppressed compared to that in wild-type mice. Importantly, in AhR-CA::ArtnΔXRE mice, Artn expression was significantly suppressed, and alloknesis was improved. These results demonstrate that the Artn gene is indeed regulated by the distal XRE-containing enhancer, and alloknesis in AhR-CA mice is provoked by the AhR-mediated direct induction of the Artn gene.

リンク情報
DOI
https://doi.org/10.1128/MCB.00190-19
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31358547
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766698
ID情報
  • DOI : 10.1128/MCB.00190-19
  • ISSN : 0270-7306
  • PubMed ID : 31358547
  • PubMed Central 記事ID : PMC6766698

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