Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF.
Liver sinusoidal endothelial cells (LSECs) represent a highly differentiated cell type that lines hepatic sinusoids. LSECs form a discontinuous endothelium due to fenestrations under physiological conditions, which are reduced upon chronic liver injury. Cultivation of rodent LSECs associates with a...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4631446?pdf=render |
| _version_ | 1818552531191595008 |
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| author | Petra Koudelkova Gerhard Weber Wolfgang Mikulits |
| author_facet | Petra Koudelkova Gerhard Weber Wolfgang Mikulits |
| author_sort | Petra Koudelkova |
| collection | DOAJ |
| description | Liver sinusoidal endothelial cells (LSECs) represent a highly differentiated cell type that lines hepatic sinusoids. LSECs form a discontinuous endothelium due to fenestrations under physiological conditions, which are reduced upon chronic liver injury. Cultivation of rodent LSECs associates with a rapid onset of stress-induced senescence a few days post isolation, which limits genetic and biochemical studies ex vivo. Here we show the establishment of LSECs isolated from p19ARF-/- mice which undergo more than 50 cell doublings in the absence of senescence. Isolated p19ARF-/- LSECs display a cobblestone-like morphology and show the ability of tube formation. Analysis of DNA content revealed a stable diploid phenotype after long-term passaging without a gain of aneuploidy. Notably, p19ARF-/- LSECs express the endothelial markers CD31, vascular endothelial growth factor receptor (VEGFR)-2, VE-cadherin, von Willebrand factor, stabilin-2 and CD146 suggesting that these cells harbor and maintain an endothelial phenotype. In line, treatment with small molecule inhibitors against VEGFR-2 caused cell death, demonstrating the sustained ability of p19ARF-/- LSECs to respond to anti-angiogenic therapeutics. From these data we conclude that loss of p19ARF overcomes senescence of LSECs, allowing immortalization of cells without losing endothelial characteristics. Thus, p19ARF-/- LSECs provide a novel cellular model to study endothelial cell biology. |
| first_indexed | 2024-12-12T09:14:25Z |
| format | Article |
| id | doaj.art-712729bc2a4c4ab7a9febd4fadf9af30 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T09:14:25Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-712729bc2a4c4ab7a9febd4fadf9af302022-12-22T00:29:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e014213410.1371/journal.pone.0142134Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF.Petra KoudelkovaGerhard WeberWolfgang MikulitsLiver sinusoidal endothelial cells (LSECs) represent a highly differentiated cell type that lines hepatic sinusoids. LSECs form a discontinuous endothelium due to fenestrations under physiological conditions, which are reduced upon chronic liver injury. Cultivation of rodent LSECs associates with a rapid onset of stress-induced senescence a few days post isolation, which limits genetic and biochemical studies ex vivo. Here we show the establishment of LSECs isolated from p19ARF-/- mice which undergo more than 50 cell doublings in the absence of senescence. Isolated p19ARF-/- LSECs display a cobblestone-like morphology and show the ability of tube formation. Analysis of DNA content revealed a stable diploid phenotype after long-term passaging without a gain of aneuploidy. Notably, p19ARF-/- LSECs express the endothelial markers CD31, vascular endothelial growth factor receptor (VEGFR)-2, VE-cadherin, von Willebrand factor, stabilin-2 and CD146 suggesting that these cells harbor and maintain an endothelial phenotype. In line, treatment with small molecule inhibitors against VEGFR-2 caused cell death, demonstrating the sustained ability of p19ARF-/- LSECs to respond to anti-angiogenic therapeutics. From these data we conclude that loss of p19ARF overcomes senescence of LSECs, allowing immortalization of cells without losing endothelial characteristics. Thus, p19ARF-/- LSECs provide a novel cellular model to study endothelial cell biology.http://europepmc.org/articles/PMC4631446?pdf=render |
| spellingShingle | Petra Koudelkova Gerhard Weber Wolfgang Mikulits Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF. PLoS ONE |
| title | Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF. |
| title_full | Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF. |
| title_fullStr | Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF. |
| title_full_unstemmed | Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF. |
| title_short | Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF. |
| title_sort | liver sinusoidal endothelial cells escape senescence by loss of p19arf |
| url | http://europepmc.org/articles/PMC4631446?pdf=render |
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