000056746 001__ 56746
000056746 005__ 20200221144253.0
000056746 0247_ $$2doi$$a10.1038/srep28770
000056746 0248_ $$2sideral$$a96117
000056746 037__ $$aART-2016-96117
000056746 041__ $$aeng
000056746 100__ $$aSevelsted Møller, L.
000056746 245__ $$aThe calcium-Activated potassium channel KCa3.1 is an important modulator of hepatic injury
000056746 260__ $$c2016
000056746 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056746 5203_ $$aThe calcium-Activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury.
000056746 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056746 590__ $$a4.259$$b2016
000056746 591__ $$aMULTIDISCIPLINARY SCIENCES$$b10 / 63 = 0.159$$c2016$$dQ1$$eT1
000056746 592__ $$a1.691$$b2016
000056746 593__ $$aMultidisciplinary$$c2016$$dQ1
000056746 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056746 700__ $$aFialla, A.D.
000056746 700__ $$aSchierwagen, R.
000056746 700__ $$aBiagini, M.
000056746 700__ $$aLiedtke, C.
000056746 700__ $$aLaleman, W.
000056746 700__ $$aKlein, S.
000056746 700__ $$aReul, W.
000056746 700__ $$aKoch Hansen, L.
000056746 700__ $$aRabjerg, M.
000056746 700__ $$aSingh, V.
000056746 700__ $$0(orcid)0000-0002-5841-0462$$aSurra, J.$$uUniversidad de Zaragoza
000056746 700__ $$0(orcid)0000-0002-8251-8457$$aOsada, J.$$uUniversidad de Zaragoza
000056746 700__ $$aReinehr, R.
000056746 700__ $$aDe Muckadell, O.B.S.
000056746 700__ $$aKöhler, R.
000056746 700__ $$aTrebicka, J.
000056746 7102_ $$12008$$2700$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Producción Animal
000056746 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000056746 773__ $$g6 (2016), 28770 [12 pp.]$$pSci. rep.$$tSCIENTIFIC REPORTS$$x2045-2322
000056746 8564_ $$s1453553$$uhttps://zaguan.unizar.es/record/56746/files/texto_completo.pdf$$yVersión publicada
000056746 8564_ $$s114601$$uhttps://zaguan.unizar.es/record/56746/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056746 909CO $$ooai:zaguan.unizar.es:56746$$particulos$$pdriver
000056746 951__ $$a2020-02-21-13:28:53
000056746 980__ $$aARTICLE