The Long Noncoding RNA Landscape in Hypoxic and Inflammatory

46 Long noncoding RNAs (lncRNAs) are emerging as key species-specific regulators of 47 cellular and disease processes. To identify potential lncRNAs relevant to acute and chronic 48 renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal 49 tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing (RNA50 seq) revealed that the protein-coding and noncoding transcriptomic landscape differed between 51 hypoxia-stimulated and cytokine-stimulated human PTECs. Hypoxiaand inflammation52 modulated lncRNAs were prioritized for focused follow up according to their degree of induction 53 by these stress stimuli, their expression in human kidney tissue, and whether exposure of 54 human PTECs to plasma of critically ill sepsis patients with acute kidney injury modulated their 55 expression. For three lncRNAs--MIR210HG, linc-ATP13A4-8, and linc-KIAA1737-2--that fulfilled 56 our criteria, we validated their expression patterns, examined their loci for conservation and 57 synteny, and defined their associated epigenetic marks. The lncRNA landscape characterized 58 here provides insight into novel transcriptomic variations in the renal epithelial cell response to 59 hypoxic and inflammatory stress. 60