Cargando…
The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury
The 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. Effec...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926059/ https://www.ncbi.nlm.nih.gov/pubmed/27354175 http://dx.doi.org/10.1038/srep28770 |
_version_ | 1782440035584311296 |
---|---|
author | Sevelsted Møller, Linda Fialla, Annette Dam Schierwagen, Robert Biagini, Matteo Liedtke, Christian Laleman, Wim Klein, Sabine Reul, Winfried Koch Hansen, Lars Rabjerg, Maj Singh, Vikrant Surra, Joaquin Osada, Jesus Reinehr, Roland de Muckadell, Ove B. Schaffalitzky Köhler, Ralf Trebicka, Jonel |
author_facet | Sevelsted Møller, Linda Fialla, Annette Dam Schierwagen, Robert Biagini, Matteo Liedtke, Christian Laleman, Wim Klein, Sabine Reul, Winfried Koch Hansen, Lars Rabjerg, Maj Singh, Vikrant Surra, Joaquin Osada, Jesus Reinehr, Roland de Muckadell, Ove B. Schaffalitzky Köhler, Ralf Trebicka, Jonel |
author_sort | Sevelsted Møller, Linda |
collection | PubMed |
description | The 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. |
format | Online Article Text |
id | pubmed-4926059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49260592016-06-29 The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury Sevelsted Møller, Linda Fialla, Annette Dam Schierwagen, Robert Biagini, Matteo Liedtke, Christian Laleman, Wim Klein, Sabine Reul, Winfried Koch Hansen, Lars Rabjerg, Maj Singh, Vikrant Surra, Joaquin Osada, Jesus Reinehr, Roland de Muckadell, Ove B. Schaffalitzky Köhler, Ralf Trebicka, Jonel Sci Rep Article The 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. Nature Publishing Group 2016-06-29 /pmc/articles/PMC4926059/ /pubmed/27354175 http://dx.doi.org/10.1038/srep28770 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Sevelsted Møller, Linda Fialla, Annette Dam Schierwagen, Robert Biagini, Matteo Liedtke, Christian Laleman, Wim Klein, Sabine Reul, Winfried Koch Hansen, Lars Rabjerg, Maj Singh, Vikrant Surra, Joaquin Osada, Jesus Reinehr, Roland de Muckadell, Ove B. Schaffalitzky Köhler, Ralf Trebicka, Jonel The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury |
title | The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury |
title_full | The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury |
title_fullStr | The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury |
title_full_unstemmed | The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury |
title_short | The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury |
title_sort | calcium-activated potassium channel kca3.1 is an important modulator of hepatic injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926059/ https://www.ncbi.nlm.nih.gov/pubmed/27354175 http://dx.doi.org/10.1038/srep28770 |
work_keys_str_mv | AT sevelstedmøllerlinda thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT fiallaannettedam thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT schierwagenrobert thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT biaginimatteo thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT liedtkechristian thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT lalemanwim thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT kleinsabine thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT reulwinfried thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT kochhansenlars thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT rabjergmaj thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT singhvikrant thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT surrajoaquin thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT osadajesus thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT reinehrroland thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT demuckadellovebschaffalitzky thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT kohlerralf thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT trebickajonel thecalciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT sevelstedmøllerlinda calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT fiallaannettedam calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT schierwagenrobert calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT biaginimatteo calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT liedtkechristian calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT lalemanwim calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT kleinsabine calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT reulwinfried calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT kochhansenlars calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT rabjergmaj calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT singhvikrant calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT surrajoaquin calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT osadajesus calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT reinehrroland calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT demuckadellovebschaffalitzky calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT kohlerralf calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury AT trebickajonel calciumactivatedpotassiumchannelkca31isanimportantmodulatorofhepaticinjury |