Title:	Conditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis
Authors:	Lozano-Gerona, Javier Olivan-Viguera, Aida Delgado-Wicke, Pablo Singh, Vikrant Brown, Brandon M. Tapia-Casellas, Elena Pueyo, Esther Valero Gracia, Marta Sofía García-Otín, Ángel Luis Giraldo, Pilar Abarca-Lachén, Edgar Surra, Joaquín Carlos E. Osada, Jesús Hamilton, Kirk L Raychaudhuri, Siba Prasad Marigil, Miguel Angel Juarranz, Ángeles Wulff, Heike Miura, Hiroto Gilaberte, Yolanda Köhler, Ralf
Keywords:	Dermatitis; KCa3.1
Issue Date:	9-Mar-2020
Publisher:	Public Library of Science
Citation:	Lozano-Gerona J, Oliván-Viguera A, Delgado-Wicke P, Singh V, Brown BM, Tapia-Casellas E, et al. (2020) Conditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis. PLoS ONE 15(3): e0222619. https://doi.org/10.1371/journal.pone.0222619
Description:	Ion channels have recently attracted attention as potential mediators of skin disease. Here, we explored the consequences of genetically encoded induction of the cell volume-regulating Ca2+-activated KCa3.1 channel (Kcnn4) for murine epidermal homeostasis. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse tetracycline-sensitive transactivator (rtTA) showed 800-fold channel overexpression above basal levels in the skin and solid KCa3.1-currents in keratinocytes. This overexpression resulted in epidermal spongiosis, progressive epidermal hyperplasia and hyperkeratosis, itch and ulcers. The condition was accompanied by production of the pro-proliferative and pro-inflammatory cytokines, IL-β1 (60-fold), IL-6 (33-fold), and TNFα (26-fold) in the skin. Treatment of mice with the KCa3.1-selective blocker, Senicapoc, significantly suppressed spongiosis and hyperplasia, as well as induction of IL-β1 (-88%) and IL-6 (-90%). In conclusion, KCa3.1-induction in the epidermis caused expression of pro-proliferative cytokines leading to spongiosis, hyperplasia and hyperkeratosis. This skin condition resembles pathological features of eczematous dermatitis and identifies KCa3.1 as a regulator of epidermal homeostasis and spongiosis, and as a potential therapeutic target.
URI:	https://repositorio.usj.es/handle/123456789/382
ISSN:	1932-6203
Appears in Collections:	Artículos de revistas

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