5 years ago

High susceptibility of Lrig1 sebaceous stem cells to TCDD in mice.

Sorg, Fontao, Barnes, Saurat, Kaya
We have previously shown that CYP1A1 was highly induced for a long period of time in a patient who had been poisoned by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a compound known to activate the aryl hydrocarbon receptor (AhR). During that period of time no sebaceous glands could be observed in the skin of this patient. In the present study, starting from observations in the patient exposed to TCDD, we analysed the seboatrophy induced by dioxins in mice. We observed a very different pattern of AhR and CYP1A1 immunostaining in skin biopsies of the patient. When applying TCDD and beta-naphthoflavone (BNF), another AhR agonist, on the ears of C57BL/6J mice, we reproduced (i) an atrophy of sebaceous glands, (ii) a strong induction of CYP1A1 within the glands, and (iii) a dramatic repression of the genes encoding the sebogenic enzymes AWAT1, ELOVL3 and SCD1. These effects were reversible. LRIG1 expressing progenitor cells, found in the vicinity of sebaceous glands, were shown to be the initial skin cellular targets of AhR agonists. These cells retained the DNA label BrdU and co-localised with the CYP1A1 protein for at least 30 days. A downregulation of LRIG1 by siRNA in cultured sebocytes significantly decreased the CYP1A1 response to TCDD, indicating that LRIG1 contributes to a higher susceptibility of AhR agonists. In conclusion these observations provide for the first time a strong experimental support to the concept that dioxin-induced skin pathology may be driven by a molecular switch in progenitor cells involved in the physiological turnover of sebaceous glands.

Publisher URL: http://doi.org/10.1093/toxsci/kfx179

DOI: 10.1093/toxsci/kfx179

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.