89614 20210902121651.0 doi 10.1371/journal.pone.0222619 sideral 117407 ART-2020-117407 eng Lozano-Gerona, J. Conditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis 2020 Access copy available to the general public Unrestricted 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-ß1 (60-fold), IL-6 (33-fold), and TNFa (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-ß1 (-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. info:eu-repo/grantAgreement/ES/DGA/B04-17R info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS info:eu-repo/grantAgreement/EUR/FP7/PEOPLE-MC-CIG info:eu-repo/grantAgreement/EC/H2020/638284/EU/Is your heart aging well? A systems biology approach to characterize cardiac aging from the cell to the body surface/MODELAGE This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 638284-MODELAGE info:eu-repo/grantAgreement/ES/ISCIII/FIS-CB06-07-1036 info:eu-repo/grantAgreement/ES/ISCIII/FIS-PI16-02112 info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.24 2020 MULTIDISCIPLINARY SCIENCES 26 / 73 = 0.356 2020 Q2 T2 0.99 2020 Multidisciplinary 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Oliván-Viguera, A. (orcid)0000-0001-5348-924X Delgado-Wicke, P. Singh, V. Brown, B.M. Tapia-Casellas, E. Universidad de Zaragoza Pueyo, E. Universidad de Zaragoza (orcid)0000-0002-1960-407X Valero, M.S. Universidad de Zaragoza (orcid)0000-0002-2231-7565 Garcia-Otín, Á.L. Giraldo, P. Abarca-Lachen, E. Surra, J.C. Universidad de Zaragoza (orcid)0000-0002-5841-0462 Osada, J. Universidad de Zaragoza (orcid)0000-0002-8251-8457 Hamilton, K.L. Raychaudhuri, S.P. Marigil, M. Juarranz, Á. Wulff, H. Miura, H. Gilaberte, Y. Universidad de Zaragoza (orcid)0000-0001-8034-3617 Köhler, R. 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 2008 700 Universidad de Zaragoza Dpto. Produc.Animal Cienc.Ali. Área Producción Animal 0 X Universidad de Zaragoza Serv.Gral. Apoyo Investigación Servicios. División Biomédica 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1007 183 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Área Dermatología 15, 3 (2020), e0222619 [18 pp.] PLoS One PloS one 1932-6203 3322235 http://zaguan.unizar.es/record/89614/files/texto_completo.pdf Versión publicada 543755 http://zaguan.unizar.es/record/89614/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:89614 articulos driver 2021-09-02-09:06:54 ARTICLE