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Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injur...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821887/ https://www.ncbi.nlm.nih.gov/pubmed/29467431 http://dx.doi.org/10.1038/s41598-018-21720-3 |
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author | Kölling, Malte Genschel, Celina Kaucsar, Tamas Hübner, Anika Rong, Song Schmitt, Roland Sörensen-Zender, Inga Haddad, George Kistler, Andreas Seeger, Harald Kielstein, Jan T. Fliser, Danilo Haller, Hermann Wüthrich, Rudolf Zörnig, Martin Thum, Thomas Lorenzen, Johan |
author_facet | Kölling, Malte Genschel, Celina Kaucsar, Tamas Hübner, Anika Rong, Song Schmitt, Roland Sörensen-Zender, Inga Haddad, George Kistler, Andreas Seeger, Harald Kielstein, Jan T. Fliser, Danilo Haller, Hermann Wüthrich, Rudolf Zörnig, Martin Thum, Thomas Lorenzen, Johan |
author_sort | Kölling, Malte |
collection | PubMed |
description | Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was transcriptionally activated by hypoxia-inducible factor 1-α. In vitro, Malat1 inhibition reduced proliferation and the number of endothelial cells in the S-phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed similar degrees of outer medullary tubular epithelial injury, proliferation, capillary rarefaction, inflammation and fibrosis, survival and kidney function. Small-RNA sequencing and whole genome expression analysis revealed only minor changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous studies, which suggested a prominent role of Malat1 in the induction of disease, we did not confirm an in vivo role of Malat1 concerning renal I/R-injury. |
format | Online Article Text |
id | pubmed-5821887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58218872018-02-26 Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury Kölling, Malte Genschel, Celina Kaucsar, Tamas Hübner, Anika Rong, Song Schmitt, Roland Sörensen-Zender, Inga Haddad, George Kistler, Andreas Seeger, Harald Kielstein, Jan T. Fliser, Danilo Haller, Hermann Wüthrich, Rudolf Zörnig, Martin Thum, Thomas Lorenzen, Johan Sci Rep Article Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was transcriptionally activated by hypoxia-inducible factor 1-α. In vitro, Malat1 inhibition reduced proliferation and the number of endothelial cells in the S-phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed similar degrees of outer medullary tubular epithelial injury, proliferation, capillary rarefaction, inflammation and fibrosis, survival and kidney function. Small-RNA sequencing and whole genome expression analysis revealed only minor changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous studies, which suggested a prominent role of Malat1 in the induction of disease, we did not confirm an in vivo role of Malat1 concerning renal I/R-injury. Nature Publishing Group UK 2018-02-21 /pmc/articles/PMC5821887/ /pubmed/29467431 http://dx.doi.org/10.1038/s41598-018-21720-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kölling, Malte Genschel, Celina Kaucsar, Tamas Hübner, Anika Rong, Song Schmitt, Roland Sörensen-Zender, Inga Haddad, George Kistler, Andreas Seeger, Harald Kielstein, Jan T. Fliser, Danilo Haller, Hermann Wüthrich, Rudolf Zörnig, Martin Thum, Thomas Lorenzen, Johan Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury |
title | Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury |
title_full | Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury |
title_fullStr | Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury |
title_full_unstemmed | Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury |
title_short | Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury |
title_sort | hypoxia-induced long non-coding rna malat1 is dispensable for renal ischemia/reperfusion-injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821887/ https://www.ncbi.nlm.nih.gov/pubmed/29467431 http://dx.doi.org/10.1038/s41598-018-21720-3 |
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