Macrophage secretion of miR-106b-5p causes renin-dependent hypertension
| Autor: | Maria Luisa S. Sequeira-Lopez, Á Baldán, Jian Su Shao, R. A. Barve, Scot J. Matkovich, Robert P. Mecham, Mark S. Sands, Colin G. Nichols, R. A. Gomez, Hao Zhang, Russell H. Knutsen, Bruno A. Benitez, Amy E. Riek, S. M. Bindom, Kendall J. Blumer, Richard D. Head, Jisu Oh, Patrick Osei-Owusu, Carlos Bernal-Mizrachi, Geert Carmeliet |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Hypertension Renal Cell General Physics and Astronomy 030204 cardiovascular system & hematology Calcitriol receptor Mice 0302 clinical medicine Bone Marrow Renin Conditional gene knockout Macrophage Myeloid Cells Vitamin D lcsh:Science Bone Marrow Transplantation Mice Knockout Nephritis Multidisciplinary Endoplasmic Reticulum Stress Biological sciences medicine.anatomical_structure Hypertension Female medicine.medical_specialty Science Article General Biochemistry Genetics and Molecular Biology vitamin D deficiency 03 medical and health sciences Internal medicine Renin–angiotensin system Vitamin D and neurology medicine Animals Secretion business.industry Macrophages General Chemistry medicine.disease Mice Inbred C57BL Disease Models Animal MicroRNAs 030104 developmental biology Endocrinology Receptors Calcitriol lcsh:Q business E2F1 Transcription Factor |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) Nature Communications |
| Popis: | 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. Myeloid cells are involved in hypertension, but their exact role in renin-induced hypertension remains unclear. Here the authors show that impaired vitamin D signaling in myeloid cells causes hypertension via macrophage-specific miR-106b-5p secretion, which activates renin production in the kidney. |
| Databáze: | OpenAIRE |
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