Arsenic-mediated hyperpigmentation in skin via NF-kappa B/endothelin-1 signaling in an originally developed hairless mouse model.

In this study, hairless homozygous mice (Hr/Hr-mice) that drank water containing 3 and 30 µM arsenic for 2 months developed skin hyperpigmentation with increased levels of arsenic and number of melanocytes in the skin. Since it is possible for humans to be exposed to 3 µM of arsenic in well drinking water, our results suggest that the Hr/Hr-mice could be a novel model sensitively reflecting arsenic-mediated skin hyperpigmentation. We then analyzed the mechanism of arsenic-mediated skin hyperpigmentation. The epidermis of Hr/Hr-mice and human HaCaT skin keratinocytes exposed to arsenic for 2 and 4 months, respectively, showed 5.4-21.5-fold increased levels of endothelin-1 (ET-1) expression via NF-kappa B activation. Coexposure of primary normal human epithelial melanocytes to arsenic and ET-1 activated their proliferation and melanin synthesis with increased levels of MITF-M and ET-1 receptor expression. Our results suggest that interaction between keratinocytes and melanocytes in the skin through ET-1 and its receptor contributes to arsenic-mediated skin pigmentation, a hallmark of arsenicosis.
PMID: 28470405 [PubMed - as supplied by publisher]

Source: Archives of Toxicology - May 3, 2017 Category: Toxicology Authors: Yajima I, Kumasaka MY, Iida M, Oshino R, Tanihata H, Al Hossain A, Ohgami N, Kato M Tags: Arch Toxicol Source Type: research