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

Am J Physiol Renal Physiol. 2015 Dec 1;309(11):F901-13. doi: 10.1152/ajprenal.00290.2015. Epub 2015 Sep 23.

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.

Keywords: RNA sequencing; epithelial injury; hypoxia; inflammation; noncoding RNA.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Cell Hypoxia
  • Cell Line
  • Cytokines / pharmacology
  • Epigenesis, Genetic
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Genetic Markers
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Hypoxia / pathology
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation Mediators / pharmacology
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Reproducibility of Results
  • Sepsis / genetics
  • Sepsis / metabolism
  • Sepsis / pathology
  • Time Factors

Substances

  • Cytokines
  • Genetic Markers
  • Inflammation Mediators
  • RNA, Long Noncoding