Macrophage secretion of miR-106b-5p causes renin-dependent hypertension.
Nat Commun, 2020/09/23;11(1):4798.
Oh J[1], Matkovich SJ[1], Riek AE[1], Bindom SM[2], Shao JS[1], Head RD[3], Barve RA[3], Sands MS[1, 3], Carmeliet G[4], Osei-Owusu P[5], Knutsen RH[5], Zhang H[5], Blumer KJ[5], Nichols CG[5], Mecham RP[5], Baldán Á[6], Benitez BA[7], Sequeira-Lopez ML[8, 9], Gomez RA[8, 9], Bernal-Mizrachi C[10, 11, 12]
Affiliations
PMID: 32968066DOI: 10.1038/s41467-020-18538-x
Impact factor: 17.694
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.
MeSH terms
Animals; Bone Marrow; Bone Marrow Transplantation; Disease Models, Animal; E2F1 Transcription Factor; Endoplasmic Reticulum Stress; Female; Hypertension; Hypertension, Renal; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Myeloid Cells; Nephritis; Receptors, Calcitriol; Renin; Vitamin D
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