Af17 deficiency increases sodium excretion and decreases blood pressure

Lihe Chen, Hongyu Wu, Oleh M. Pochynyuk, Mary Rose Reisenauer, Zhijing Zhang, Le Huang, Oleg Leonidovych Zaika, Mykola Mamenko, Weiru Zhang, Qiaoling Zhou, Mingyao Liu, Yang Xia, Wenzheng Zhang

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18 Scopus citations

Abstract

The putative transcription factor AF17 upregulates the transcription of the epithelial sodium channel (ENaC) genes, but whether AF17 modulates sodium homeostasis and BP is unknown. Here, we generated Af17-deficient mice to determine whether deletion of Af17 leads to sodium wasting and low BP. Compared with wild-type mice, Af17-deficient mice had lower BP (11 mmHg), higher urine volume, and increased sodium excretion despite mildly increased plasma concentrations of aldosterone. Deletion of Af17 led to increased dimethylation of histone H3 K79 and reduced ENaC function. The attenuated function of ENaC resulted from decreased ENaC mRNA and protein expression, fewer active channels, lower open probability, and reduced effective activity. In contrast, inducing high levels of plasma aldosterone by a variety of methods completely compensated for Af17 deficiency with respect to sodium handling and BP. Taken together, these data identify Af17 as a potential locus for the maintenance of sodium and BP homeostasis and suggest that a particular histone modification is directly linked to these processes. Af17-mediated regulation of BP is largely, but not exclusively, the result of modulating ENaC, suggesting it has potential as a therapeutic target for the control of BP.

Original languageEnglish (US)
Pages (from-to)1076-1086
Number of pages11
JournalJournal of the American Society of Nephrology
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

Cite this

Chen, L., Wu, H., Pochynyuk, O. M., Reisenauer, M. R., Zhang, Z., Huang, L., Zaika, O. L., Mamenko, M., Zhang, W., Zhou, Q., Liu, M., Xia, Y., & Zhang, W. (2011). Af17 deficiency increases sodium excretion and decreases blood pressure. Journal of the American Society of Nephrology, 22(6), 1076-1086. https://doi.org/10.1681/ASN.2010121270