Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Fluid-electrolyte homeostasis requires histone deacetylase function
Kelly A. Hyndman, … , David M. Pollock, Jennifer S. Pollock
Kelly A. Hyndman, … , David M. Pollock, Jennifer S. Pollock
Published July 16, 2020
Citation Information: JCI Insight. 2020;5(16):e137792. https://doi.org/10.1172/jci.insight.137792.
View: Text | PDF
Research Article Cell biology Nephrology

Fluid-electrolyte homeostasis requires histone deacetylase function

  • Text
  • PDF
Abstract

Histone deacetylase (HDAC) enzymes regulate transcription through epigenetic modification of chromatin structure, but their specific functions in the kidney remain elusive. We discovered that the human kidney expresses class I HDACs. Kidney medulla-specific inhibition of class I HDACs in the rat during high-salt feeding results in hypertension, polyuria, hypokalemia, and nitric oxide deficiency. Three new inducible murine models were used to determine that HDAC1 and HDAC2 in the kidney epithelium are necessary for maintaining epithelial integrity and maintaining fluid-electrolyte balance during increased dietary sodium intake. Moreover, single-nucleus RNA-sequencing determined that epithelial HDAC1 and HDAC2 are necessary for expression of many sodium or water transporters and channels. In performing a systematic review and meta-analysis of serious adverse events associated with clinical HDAC inhibitor use, we found that HDAC inhibitors increased the odds ratio of experiencing fluid-electrolyte disorders, such as hypokalemia. This study provides insight on the mechanisms of potential serious adverse events with HDAC inhibitors, which may be fatal to critically ill patients. In conclusion, kidney tubular HDACs provide a link between the environment, such as consumption of high-salt diets, and regulation of homeostatic mechanisms to remain in fluid-electrolyte balance.

Authors

Kelly A. Hyndman, Joshua S. Speed, Luciano D. Mendoza, John M. Allan, Jackson Colson, Randee Sedaka, Chunhua Jin, Hyun Jun Jung, Samir El-Dahr, David M. Pollock, Jennifer S. Pollock

×

Graphical abstract

Options: View larger image (or click on image)

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts