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 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.

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Author:Malte Kölling, Celina Genschel, Tamas Kaucsar, Anika Hübner, Song Rong, Roland Schmitt, Inga Sörensen-Zender, George Haddad, Andreas Kistler, Harald Seeger, Jan T. KielsteinORCiDGND, Danilo Fliser, Hermann Haller, Rudolf Wüthrich, Martin ZörnigORCiD, Thomas ThumORCiDGND, Johan Lorenzen
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29467431
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/02/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/03/13
Issue:1, Art. 3438
Page Number:14
First Page:1
Last Page:14
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/.
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0