000078847 001__ 78847
000078847 005__ 20210820090345.0
000078847 0247_ $$2doi$$a10.3390/ijms20051193
000078847 0248_ $$2sideral$$a111132
000078847 037__ $$aART-2019-111132
000078847 041__ $$aeng
000078847 100__ $$0(orcid)0000-0002-2231-7565$$aValero Gracia, Marta Sofía$$uUniversidad de Zaragoza
000078847 245__ $$aKCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility.
000078847 260__ $$c2019
000078847 5060_ $$aAccess copy available to the general public$$fUnrestricted
000078847 5203_ $$aAbstract: The epithelial intermediate-conductance calcium/calmodulin-regulated KCa3.1 channel is considered to be a regulator of intestine function by controlling chloride secretion and water/salt balance. Yet, little is known about the functional importance of KCa3.1 in the intestinal epithelium in vivo. Our objective was to determine the impact of epithelial-specific inducible overexpression of a KCa3.1 transgene (KCa3.1+) and of inducible suppression (KCa3.1-) on intestinal homeostasis and function in mice. KCa3.1 overexpression in the duodenal epithelium of doxycycline (DOX)-treated KCa3.1+ mice was 40-fold above the control levels. Overexpression caused an inflated duodenum and doubling of the chyme content. Histology showed conserved architecture of crypts, villi, and smooth muscle. Unaltered proliferating cell nuclear antigen (PCNA) immune reactivity and reduced amounts of terminal deoxynucleotide transferase mediated X-dUTP nick end labeling (TUNEL)-positive apoptotic cells in villi indicated lower epithelial turnover. Myography showed a reduction in the frequency of spontaneous propulsive muscle contractions with no change in amplitude. The amount of stool in the colon was increased and the frequency of colonic contractions was reduced in KCa3.1+ animals. Senicapoc treatment prevented the phenotype. Suppression of KCa3.1 in DOX-treated KCa3.1- mice caused no overt intestinal phenotype. In conclusion, inducible KCa3.1 overexpression alters intestinal functions by increasing the chyme content and reducing spontaneous contractions and epithelial apoptosis. Induction of epithelial KCa3.1 can play a mechanistic role in the process of adaptation of the intestine.
000078847 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS-PI16-02112$$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/METIC$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS$$9info:eu-repo/grantAgreement/ES/DGA/C072-2014$$9info:eu-repo/grantAgreement/ES/DGA/B04-17R
000078847 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000078847 590__ $$a4.556$$b2019
000078847 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b48 / 177 = 0.271$$c2019$$dQ2$$eT1
000078847 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b74 / 297 = 0.249$$c2019$$dQ1$$eT1
000078847 592__ $$a1.317$$b2019
000078847 593__ $$aMedicine (miscellaneous)$$c2019$$dQ1
000078847 593__ $$aPhysical and Theoretical Chemistry$$c2019$$dQ1
000078847 593__ $$aComputer Science Applications$$c2019$$dQ1
000078847 593__ $$aInorganic Chemistry$$c2019$$dQ1
000078847 593__ $$aSpectroscopy$$c2019$$dQ1
000078847 593__ $$aOrganic Chemistry$$c2019$$dQ1
000078847 593__ $$aMolecular Biology$$c2019$$dQ2
000078847 593__ $$aCatalysis$$c2019$$dQ2
000078847 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000078847 700__ $$aRamón Gimenez, Mariano
000078847 700__ $$aLozano-Gerona, Javier
000078847 700__ $$aDelgado-Wicke, Pablo
000078847 700__ $$aCalmarza, Pilar
000078847 700__ $$0(orcid)0000-0001-5348-924X$$aOlivan-Viguera, Aida
000078847 700__ $$0(orcid)0000-0001-6969-1055$$aLópez, Víctor
000078847 700__ $$0(orcid)0000-0002-5123-2480$$aGarcía-Otín, Luís-Ángel
000078847 700__ $$aValero, Salvador
000078847 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000078847 700__ $$aHamilton, Kir
000078847 700__ $$aMiura, Hioto
000078847 700__ $$0(orcid)0000-0002-0833-9717$$aKöhler, Ralf
000078847 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología
000078847 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000078847 773__ $$g20, 5 (2019), 1193$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000078847 8564_ $$s646340$$uhttps://zaguan.unizar.es/record/78847/files/texto_completo.pdf$$yVersión publicada
000078847 8564_ $$s108721$$uhttps://zaguan.unizar.es/record/78847/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000078847 909CO $$ooai:zaguan.unizar.es:78847$$particulos$$pdriver
000078847 951__ $$a2021-08-20-08:37:41
000078847 980__ $$aARTICLE