Macrophage secretion of miR-106b-5p causes renin-dependent hypertension

J. Oh, S. J. Matkovich, A. E. Riek, S. M. Bindom, J. S. Shao, R. D. Head, R. A. Barve, M. S. Sands, G. Carmeliet, P. Osei-Owusu, R. H. Knutsen, H. Zhang, K. J. Blumer, C. G. Nichols, R. P. Mecham, Á Baldán, B. A. Benitez, M. L. Sequeira-Lopez, R. A. Gomez and C. Bernal-Mizrachi ()
Additional contact information
J. Oh: Washington University School of Medicine
S. J. Matkovich: Washington University School of Medicine
A. E. Riek: Washington University School of Medicine
S. M. Bindom: Washington University School of Medicine
J. S. Shao: Washington University School of Medicine
R. D. Head: Washington University School of Medicine
R. A. Barve: Washington University School of Medicine
M. S. Sands: Washington University School of Medicine
G. Carmeliet: KU Leuven
P. Osei-Owusu: Washington University School of Medicine
R. H. Knutsen: Washington University School of Medicine
H. Zhang: Washington University School of Medicine
K. J. Blumer: Washington University School of Medicine
C. G. Nichols: Washington University School of Medicine
R. P. Mecham: Washington University School of Medicine
Á Baldán: Saint Louis University
B. A. Benitez: Washington University School of Medicine
M. L. Sequeira-Lopez: University of Virginia School of Medicine
R. A. Gomez: University of Virginia School of Medicine
C. Bernal-Mizrachi: Washington University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b−/− bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18538-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18538-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18538-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().