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Sci Rep. 2019 Jan 24;9(1):545. doi: 10.1038/s41598-018-36921-z.

Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function.

Author information

1
Indiana University School of Medicine, Riley Children's Hospital, Indianapolis, Indiana, United States. visaxena@iu.edu.
2
The Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States.
3
The Research Institute at Nationwide Children's, Center for Clinical and Translational Research, Columbus, Ohio, and College of Medicine, Ohio State University, Columbus, Ohio, United States.
4
Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, Ohio, United States.
5
Innate Immunity Translational Research Center, Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, United States.
6
Indiana University School of Medicine, Riley Children's Hospital, Indianapolis, Indiana, United States.
7
Division of Nephrology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, United States.
8
University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York, United States.
9
Research Institute at Nationwide Children's Hospital Flow Cytometry Core Laboratory, Columbus, Ohio, United States.
10
Department of Physics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio, United States.
11
Genomics Shared Resource, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States.
12
Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States.
13
Indiana University School of Medicine, Riley Children's Hospital, Indianapolis, Indiana, United States. dhains@iu.edu.
14
Indiana University School of Medicine, Riley Children's Hospital, Indianapolis, Indiana, United States. Schwadea@iu.edu.

Abstract

The renal collecting duct consists of intercalated cells (ICs) and principal cells (PCs). We have previously demonstrated that collecting ducts have a role in the innate immune defense of the kidney. Transcriptomics is an important tool used to enhance systems-level understanding of cell biology. However, transcriptomics performed on whole kidneys provides limited insight of collecting duct cell gene expression, because these cells comprise a small fraction of total kidney cells. Recently we generated reporter mouse models to enrich collecting duct specific PC and ICs and reported targeted gene expression of anti-microbial peptide genes. Here we report transcriptomics on enriched ICs and PCs and performed a pilot study sequencing four single ICs. We identified 3,645 genes with increased relative expression in ICs compared to non-ICs. In comparison to non-PCs, 2,088 genes had higher relative expression in PCs. IC associated genes included the innate interleukin 1 receptor, type 1 and the antimicrobial peptide(AMP) adrenomedullin. The top predicted canonical pathway for enriched ICs was lipopolysaccharide/Interleukin 1 mediated inhibition of Retinoid X Receptor alpha function and decreased Retinoid X Receptor expression was confirmed to occur 1-hour post experimental murine UTI in ICs but not in non-ICs.

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