Please use this identifier to cite or link to this item: https://repositorio.usj.es/handle/123456789/382

Title: Conditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis
Authors: Lozano-Gerona, Javier ORCID SCOPUSID
Olivan-Viguera, Aida ORCID RESEARCHERID
Delgado-Wicke, Pablo ORCID SCOPUSID
Singh, Vikrant SCOPUSID
Brown, Brandon M. ORCID SCOPUSID
Tapia-Casellas, Elena SCOPUSID
Pueyo, Esther ORCID RESEARCHERID SCOPUSID
Valero Gracia, Marta Sofía ORCID SCOPUSID
García-Otín, Ángel Luis ORCID RESEARCHERID SCOPUSID
Giraldo, Pilar ORCID RESEARCHERID SCOPUSID
Abarca-Lachén, Edgar ORCID RESEARCHERID SCOPUSID
Surra, Joaquín Carlos E. ORCID SCOPUSID
Osada, Jesús ORCID SCOPUSID
Hamilton, Kirk L SCOPUSID
Raychaudhuri, Siba Prasad SCOPUSID
Marigil, Miguel Angel SCOPUSID
Juarranz, Ángeles ORCID SCOPUSID
Wulff, Heike ORCID SCOPUSID
Miura, Hiroto SCOPUSID
Gilaberte, Yolanda ORCID RESEARCHERID SCOPUSID
Köhler, Ralf ORCID SCOPUSID
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



This item is licensed under a Creative Commons License Creative Commons