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Author Notes:

Address for correspondence: Dr. Jeff M. Sands, Emory University School of Medicine, Renal Division, 101 Woodruff Circle, WMB 338, Atlanta, GA 30322 USA, Phone: 404-727-3959, FAX: 404-727-3425, jeff.sands@emory.edu

Thanks to Gregory Tharp and Steve Bosinger at the Yerkes National Primate Center RNA sequencing core for help with interpretation of the microRNA seq data.

Disclosures: No conflicts of interest are declared by the authors.

Subjects:

Research Funding:

This work was supported by NIH grants DK41707 and DK89828.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, General & Internal
  • General & Internal Medicine
  • Urine concentration
  • microRNA
  • Quantitative polymerase chain reaction
  • Dehydration
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • UT-B
  • MIR-200 FAMILY
  • MAMMALIAN KIDNEY
  • RENAL FIBROSIS
  • SMALL RNAS
  • E-CADHERIN
  • C-ELEGANS
  • ERYTHROCYTES
  • EXPRESSION

Urea Transporter B and MicroRNA-200c Differ in Kidney Outer Versus Inner Medulla Following Dehydration

Tools:

Journal Title:

American Journal of the Medical Sciences

Volume:

Volume 352, Number 3

Publisher:

, Pages 296-301

Type of Work:

Article | Post-print: After Peer Review

Abstract:

BACKGROUND: Urea transporters (UTs) are important in urine concentration and in urea recycling, and UT-B has been implicated in both. In kidney, UT-B was originally localized to outer medullary descending vasa recta, and more recently detected in inner medullary descending vasa recta. Endogenously produced microRNAs (miRs) bind to the 3'UTR of genes and generally inhibit their translation, thus playing a pivotal role gene regulation. METHODS: Mice were dehydrated for 24 hours then sacrificed. Inner and outer medullas were analyzed by polymerase chain reaction (PCR) and quantitative PCR for miRNA expression and analyzed by western blotting for protein abundance. RESULTS: MiRNA sequencing analysis of mouse inner medullas showed a 40% increase in miRNA-200c in dehydrated mice compared with controls. An in silico analysis of the targets for miR-200c revealed that miRNA-200c could directly target the gene for UT-B. PCR confirmed that miR-200c is up-regulated in the inner medullas of dehydrated mice while western blot showed that UT-B protein abundance was down-regulated in the same portion of the kidney. However, in the outer medulla, miR-200c was reduced and UT-B protein was increased in dehydrated mice. CONCLUSIONS: This is the first indication that UT-B protein and miR-200c may each be differentially regulated by dehydration within the kidney outer and inner medulla. The inverse correlation between the direction of change in miR-200c and UT-B protein abundance in both the inner and outer medulla suggests that miR-200c may be associated with the change in UT-B protein in these 2 portions of the kidney medulla.

Copyright information:

© 2016 Southern Society for Clinical Investigation

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