Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury

Sci Rep. 2018 Feb 21;8(1):3438. doi: 10.1038/s41598-018-21720-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / pathology
  • Animals
  • Cell Line
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Long Noncoding / genetics*
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / pathology
  • Transcriptional Activation*

Substances

  • MALAT1 long non-coding RNA, human
  • Malat1 long non-coding RNA, mouse
  • RNA, Long Noncoding