000089614 001__ 89614
000089614 005__ 20210902121651.0
000089614 0247_ $$2doi$$a10.1371/journal.pone.0222619
000089614 0248_ $$2sideral$$a117407
000089614 037__ $$aART-2020-117407
000089614 041__ $$aeng
000089614 100__ $$aLozano-Gerona, J.
000089614 245__ $$aConditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis
000089614 260__ $$c2020
000089614 5060_ $$aAccess copy available to the general public$$fUnrestricted
000089614 5203_ $$aIon 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.
000089614 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS-PI16-02112$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS-CB06-07-1036$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 638284-MODELAGE$$9info:eu-repo/grantAgreement/EC/H2020/638284/EU/Is your heart aging well? A systems biology approach to characterize cardiac aging from the cell to the body surface/MODELAGE$$9info:eu-repo/grantAgreement/EUR/FP7/PEOPLE-MC-CIG$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS$$9info:eu-repo/grantAgreement/ES/DGA/B04-17R
000089614 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000089614 590__ $$a3.24$$b2020
000089614 591__ $$aMULTIDISCIPLINARY SCIENCES$$b26 / 73 = 0.356$$c2020$$dQ2$$eT2
000089614 592__ $$a0.99$$b2020
000089614 593__ $$aMultidisciplinary$$c2020$$dQ1
000089614 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000089614 700__ $$0(orcid)0000-0001-5348-924X$$aOliván-Viguera, A.
000089614 700__ $$aDelgado-Wicke, P.
000089614 700__ $$aSingh, V.
000089614 700__ $$aBrown, B.M.
000089614 700__ $$aTapia-Casellas, E.$$uUniversidad de Zaragoza
000089614 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, E.$$uUniversidad de Zaragoza
000089614 700__ $$0(orcid)0000-0002-2231-7565$$aValero, M.S.$$uUniversidad de Zaragoza
000089614 700__ $$aGarcia-Otín, Á.L.
000089614 700__ $$aGiraldo, P.
000089614 700__ $$aAbarca-Lachen, E.
000089614 700__ $$0(orcid)0000-0002-5841-0462$$aSurra, J.C.$$uUniversidad de Zaragoza
000089614 700__ $$0(orcid)0000-0002-8251-8457$$aOsada, J.$$uUniversidad de Zaragoza
000089614 700__ $$aHamilton, K.L.
000089614 700__ $$aRaychaudhuri, S.P.
000089614 700__ $$aMarigil, M.
000089614 700__ $$aJuarranz, Á.
000089614 700__ $$aWulff, H.
000089614 700__ $$aMiura, H.
000089614 700__ $$0(orcid)0000-0001-8034-3617$$aGilaberte, Y.$$uUniversidad de Zaragoza
000089614 700__ $$aKöhler, R.
000089614 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000089614 7102_ $$12008$$2700$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Producción Animal
000089614 7102_ $$10$$2X$$aUniversidad de Zaragoza$$bServ.Gral. Apoyo Investigación$$cServicios. División Biomédica
000089614 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000089614 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000089614 7102_ $$11007$$2183$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cÁrea Dermatología
000089614 773__ $$g15, 3 (2020), e0222619 [18 pp.]$$pPLoS One$$tPloS one$$x1932-6203
000089614 8564_ $$s3322235$$uhttps://zaguan.unizar.es/record/89614/files/texto_completo.pdf$$yVersión publicada
000089614 8564_ $$s543755$$uhttps://zaguan.unizar.es/record/89614/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000089614 909CO $$ooai:zaguan.unizar.es:89614$$particulos$$pdriver
000089614 951__ $$a2021-09-02-09:06:54
000089614 980__ $$aARTICLE