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

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.

Noncoding RNAs in acute kidney injury

“…This finding was further confirmed in TECs treated with plasma of critically ill sepsis AKI patients (J. Lin et al, 2015). A Q-PCR-based diseaserelated lncRNA array identifies that among 83 disease-related lncRNAs, 28 lncRNAs are upregulated and 55 lncRNAs are downregulated in TEC under hypoxia , others also detect 5,361 upregulated lncRNAs and 5,928 downregulated lncRNAs in the septic AKI group compared with control (Chun-Mei, Qin-Min, Shu-Ming, & Xiang-Yang, 2016).…”

“…J. Lin et al (2015) identified the noncoding transcriptomic landscape of human TECs in hypoxia and inflammation conditions, where MIR210HG and linc-ATP13A4-8 were induced by hypoxia while MIR210HG and linc-KIAA1737-2 were induced by inflammatory cytokines. This finding was further confirmed in TECs treated with plasma of critically ill sepsis AKI patients (J.…”

Noncoding RNA and epigenetic gene regulation in renal diseases

“…In an unbiased profiling study to identify lncRNAs that are modulated during renal tubular epithelial cell responses to hypoxia and inflammatory stimuli, Lin et al [89] identified several differentially expressed lncRNAs. Of these, modulation of MIR210HG, linc-ATP13A4-8, and linc-KIAA1737-2 abundance was confirmed in human tubular epithelial cells isolated from transplant biopsies as well as in epithelial cells exposed to plasma from patients with sepsis [89].…”

“…Of these, modulation of MIR210HG, linc-ATP13A4-8, and linc-KIAA1737-2 abundance was confirmed in human tubular epithelial cells isolated from transplant biopsies as well as in epithelial cells exposed to plasma from patients with sepsis [89]. Although a specific role for these lncRNAs has not been attributed, pathway and loci analyses were indicative of their involvement in biological pathways related to cellular stress and inflammatory response.…”

New insights into molecular mechanisms of epigenetic regulation in kidney disease

“…77 Hypoxia-and inflammation-modulated lncRNAs have also emerged as key species-specific regulators of cellular and disease processes. 79 For example, RNA-seq of human proximal tubular epithelial cells under hypoxic and inflammatory conditions to identify potential lncRNAs relevant to acute and chronic renal epithelial injury revealed changes in the expression of three lncRNAs under hypoxic and inflammatory conditions. In the same study, the loci of these lncRNAs were determined and associated epigenetic marks were defined.…”