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Glucocorticoids Reduce Renal NHE8 Expression.

Catherine Joseph1, Jyothsna Gattineni, Vangipuram Dwarakanath

  • 1Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas Dallas, Texas 75235-9063.

Physiological Reports
|September 14, 2013
PubMed
Summary
This summary is machine-generated.

Glucocorticoids, like dexamethasone, trigger a premature switch from NHE8 to NHE3 in developing kidneys. This hormonal effect reduces kidney NHE8 expression and activity, impacting bicarbonate reabsorption.

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Published on: April 25, 2016

Area of Science:

  • Nephrology
  • Molecular Biology
  • Developmental Biology

Background:

  • The proximal tubule is crucial for bicarbonate reabsorption, largely mediated by sodium-hydrogen exchangers (NHE).
  • A developmental switch from NHE8 to NHE3 isoforms occurs postnatally, coinciding with rising glucocorticoid levels.

Purpose of the Study:

  • To investigate the role of glucocorticoids in the developmental switch of renal NHE isoforms.
  • To determine if glucocorticoids directly influence NHE8 expression and activity in renal epithelial cells.

Main Methods:

  • Administration of dexamethasone to neonatal mice prior to the natural isoform switch.
  • Quantitative analysis of NHE3 and NHE8 mRNA, total protein, and brush border membrane protein abundance in mouse kidneys.
  • In vitro studies using NRK cells expressing NHE8 to assess the direct effects of dexamethasone on NHE8 expression and sodium-hydrogen exchanger activity.

Main Results:

  • Dexamethasone treatment led to a premature increase in renal NHE3 and a decrease in NHE8 mRNA, total protein, and brush border membrane protein abundance.
  • In vitro, dexamethasone reduced NHE8 mRNA, total protein, and apical protein abundance in NRK cells.
  • Dexamethasone treatment also decreased overall sodium-hydrogen exchanger activity in the studied cells.

Conclusions:

  • Glucocorticoids appear to play a significant role in mediating the developmental isoform switch from NHE8 to NHE3 in the kidney.
  • Dexamethasone directly suppresses NHE8 expression and activity in renal epithelial cells, suggesting a direct hormonal regulation mechanism.