title: 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.
authors.affiliation: Renal Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; linjenn@mail.med.upenn.edu.
authors.forename: Jennie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Chenyi
authors.initials: C
authors.lastname: Xue
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Hanrui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and.
authors.forename: Michael G S
authors.initials: MG
authors.lastname: Shashaty
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Sager J
authors.initials: SJ
authors.lastname: Gosai
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and.
authors.forename: Nuala
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Renal Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Alison
authors.initials: A
authors.lastname: Grazioli
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Christine
authors.initials: C
authors.lastname: Hinkle
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Caughey
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Renal Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gregory
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D018805:Sepsis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D005819:Genetic Markers; D018836:Inflammation Mediators; D062085:RNA, Long Noncoding
keywords: RNA sequencing; epithelial injury; hypoxia; inflammation; noncoding RNA