The long noncoding RNA landscape in hypoxic and inflammatory renal epithelial injury

Jennie Lin*, Xuan Zhang, Chenyi Xue, Hanrui Zhang, Michael G.S. Shashaty, Sager J. Gosai, Nuala Meyer, Alison Grazioli, Christine Hinkle, Jennifer Caughey, Wenjun Li, Katalin Susztak, Brian D. Gregory, Mingyao Li, Muredach P. Reilly

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Long noncoding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To identify potential lncRNAs relevant to acute and chronic renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing revealed that the protein-coding and noncoding transcriptomic landscape differed between hypoxia-stimulated and cytokine-stimulated human PTECs. Hypoxia- and inflammation-modulated lncRNAs were prioritized for focused followup according to their degree of induction by these stress stimuli, their expression in human kidney tissue, and whether exposure of human PTECs to plasma of critically ill sepsis patients with acute kidney injury modulated their expression. For three lncRNAs (MIR210HG, linc-ATP13A4-8, and linc- KIAA1737-2) that fulfilled our criteria, we validated their expression patterns, examined their loci for conservation and synteny, and defined their associated epigenetic marks. The lncRNA landscape characterized here provides insights into novel transcriptomic variations in the renal epithelial cell response to hypoxic and inflammatory stress.

Original languageEnglish (US)
Pages (from-to)F901-F913
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number11
DOIs
StatePublished - 2015

Keywords

  • Epithelial injury
  • Hypoxia
  • Inflammation
  • Noncoding RNA
  • RNA sequencing

ASJC Scopus subject areas

  • Physiology
  • Urology

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