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The Long Non-coding RNA HOTAIR Controls the Self-renewal, Cell Senescence, and Secretion of Anti-aging Protein α-Klotho in Human Adult Renal Progenitor Cells.

Authors
  • Picerno, Angela1
  • Giannuzzi, Francesca1
  • Curci, Claudia2
  • De Palma, Giuseppe3
  • Di Chiano, Mariagiovanna4
  • Simone, Simona2
  • Franzin, Rossana2, 5
  • Gallone, Anna4, 5
  • Di Lorenzo, Vito Francesco6
  • Stasi, Alessandra2, 5
  • Pertosa, Giovanni Battista2, 5
  • Sabbà, Carlo1
  • Gesualdo, Loreto2, 5
  • Sallustio, Fabio1, 5
  • 1 Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy. , (Italy)
  • 2 Nephrology, Dialysis and Transplantation Unit, DETO, University of Bari Aldo Moro, Bari, Italy. , (Italy)
  • 3 Institutional BioBank, Experimental Oncology and Biobank Management Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy, Bari, Italy. , (Italy)
  • 4 Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy. , (Italy)
  • 5 MIRROR-Medical Institute for Regeneration, Repairing and Organ Replacement, Interdepartmental Center, University of Bari Aldo Moro, Bari, Italy. , (Italy)
  • 6 Urology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. , (Italy)
Type
Published Article
Journal
The International Journal Of Cell Cloning
Publisher
Wiley (John Wiley & Sons)
Publication Date
Oct 21, 2022
Volume
40
Issue
10
Pages
963–975
Identifiers
DOI: 10.1093/stmcls/sxac054
PMID: 35922038
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The long non-coding RNAs (lncRNA) play an important role in several biological processes, including some renal diseases. Nevertheless, little is known about lncRNA that are expressed in the healthy kidneys and involved in renal cell homeostasis and development, and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs) that have been shown to be very important for renal homeostasis and repair processes. Through a whole-genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved in cell cycle and senescence biological processes. By CRISPR/Cas9 genome editing, we generated HOTAIR knockout ARPC lines and established a key role of this lncRNA in ARPC self-renewal properties by sustaining their proliferative capacity and limiting the apoptotic process. Intriguingly, the HOTAIR knockout led to the ARPC senescence and to a significant decrease in the CD133 stem cell marker expression which is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Furthermore, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6-fold higher levels compared to that secreted by renal proximal tubular cells (RPTECs). Finally, we showed that HOTAIR exerts its function through the epigenetic silencing of the cell cycle inhibitor p15 inducing the trimethylation of the histone H3K27. Altogether, these results shed new light on the mechanisms of regulation of these important renal cells and may support the future development of precision therapies for kidney diseases. © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

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