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From the Cover: High Susceptibility of Lrig1 Sebaceous Stem Cells to TCDD in Mice

Published in Toxicological Sciences. 2017, vol. 160, no. 2, p. 230-243
Abstract We have previously shown that cytochrome P450 1A1 (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 this study, starting from observations in the patient exposed to TCDD, we analyzed 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, another AhR agonist, on the ears of C57BL/6J mice, we reproduced (1) an atrophy of sebaceous glands, (2) a strong induction of CYP1A1 within the glands, and (3) a dramatic repression of the genes encoding the sebogenic enzymes AWAT1, ELOVL3, and SCD1. These effects were reversible. Leucine-rich repeats and immunoglobulin- like domains protein 1 (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 colocalized 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.
Keywords AhRDioxinCYP1A1Lrig1Progenitor cellsSebaceous glands
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Research groups La recherche en biochimie dermatologique (652)
Rôle du CD44 (809)
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FONTAO, Fabienne et al. From the Cover: High Susceptibility of Lrig1 Sebaceous Stem Cells to TCDD in Mice. In: Toxicological Sciences, 2017, vol. 160, n° 2, p. 230-243. doi: 10.1093/toxsci/kfx179 https://archive-ouverte.unige.ch/unige:99736

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Deposited on : 2017-11-28

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