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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 2 / genetics
  • Aquaporin 2 / metabolism
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression Profiling / methods*
  • Immunity, Innate / genetics
  • Interleukin-1 / metabolism
  • Kidney Tubules, Collecting / cytology*
  • Kidney Tubules, Collecting / immunology*
  • Lipopolysaccharides / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pilot Projects
  • Retinoid X Receptor alpha / antagonists & inhibitors*
  • Retinoid X Receptor alpha / metabolism*
  • Signal Transduction / genetics
  • Transcriptome / immunology
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • Aqp2 protein, mouse
  • Aquaporin 2
  • Interleukin-1
  • Lipopolysaccharides
  • Retinoid X Receptor alpha
  • Atp6v1b1 protein, mouse
  • Vacuolar Proton-Translocating ATPases