Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 39, Issue 20, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00190-19
Keywords
AhR; alloknesis; artemin; atopic dermatitis; skin
Categories
Funding
- MEXT/JSPS KAKENHI [26111002, 19H05649]
- AMED-CREST, AMED
- JSPS Research Fellowship for Young Scientists [19J10035]
- Grants-in-Aid for Scientific Research [19J10035, 19H05649] Funding Source: KAKEN
Ask authors/readers for more resources
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 Ann 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 Artn(Delta)(XRE) 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::Artn (Delta)(XRE )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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available