Class A scavenger receptor MARCO negatively regulates Ace expression and aldosterone production
- Department of Physiology, Anatomy, & Genetics, University of Oxford, United Kingdom
- Internal Medicine Department, University of Sao Paulo, Brazil
- College of Medicine, Chang Gung University, Taiwan
- Sir William Dunn School of Pathology, University of Oxford, United Kingdom
Figures
Figure 1
Marco-deficient mice have elevated aldosterone and reduced serum cholesterol.
(A) Schematic depicting the murine adrenal corticosteroid biosynthetic pathway. Plasma aldosterone and corticosterone concentrations from wild-type (WT) and Marco-deficient male (B, C) and female (D, E) mice as measured by ELISA. (F, G) Weights of both adrenal glands from WT or Marco-deficient male and female mice. Plasma total cholesterol levels (H) and relative intra-adrenal cholesterol levels, normalised to adrenal weight (I), in WT and Marco-deficient male mice. Data in B–H were analysed by two-tailed unpaired Student’s t-test and are shown as average ± SEM. *p < 0.05, **p < 0.01, ****p < 0.0001, ns = not significant.
Figure 2
Marco is expressed in the lung and not adrenal glands.
(A) Single-cell RNA-seq data plots from PMID 33571131 representing mRNA expression of Ptprc (CD45), Adgre1 (F4/80), Cd68, and Marco, in male murine adrenal glands. (B) Representative image showing a central cryosection of the male murine adrenal gland from a C57bl/6 mouse stained against CD68 (green) Marco (magenta), and DAPI (cyan). (C) Single-cell RNA-seq data plots from PMID 30283141 representing mRNA expression of Ptprc (CD45), Adgre1 (F4/80), Cd68, and Marco, in the male murine lung. (D) Representative image showing a cryosection of the male murine lung from a hCD68-GFP reporter mouse stained against GFP (green) Marco (magenta), and DAPI (cyan). (E) qPCR data showing the relative gene expression data for Marco in the indicated tissues. M = medulla, ZF = zona fasciculata, ZG = zona glomerulosa. Data in E were analysed by two-tailed unpaired Student’s t-test and are shown as average ± SEM. ****p < 0.0001, ns = not significant.
Figure 3
Marco-mediated elevation of aldosterone is not explained by upregulation of adrenal biosynthetic enzymes, the zona fasciculata, or renin.
qPCR data reporting the expression of adrenal corticosteroid biosynthetic enzymes between wild-type (WT) and Marco-deficient male mice in male (A) and female (B) mice. (C) A schematic illustrating that pituitary-derived adrenocorticotropic hormone (ACTH) stimulates the upregulation of Cyp11b1 from the zona fasciculata (ZF) and the dexamethasone-mediated suppression of this effect. (D) A bar graph showing the plasma aldosterone concentrations of Marco-deficient mice treated with vehicle or dexamethasone-supplemented drinking water for 14 days. (E) A bar graph showing the plasma renin activity of WT and Marco-deficient mice at steady state. All data were analysed by two-tailed unpaired Student’s t-test and are shown as average ± SEM. ns p > 0.05. ns = not significant.
Figure 4
Marco-deficient mice have enhanced expression of Ace in the lung.
(A) qPCR data reporting the expression of angiotensin-converting enzyme (Ace) in the lungs of wild-type (WT) and Marco-deficient male and female mice. (B) Representative images showing a cryosection of WT and Marco-deficient male murine lungs stained against ACE (green) CD68 (magenta), MARCO (yellow) and DAPI (blue). Quantitation of DAPI-normalised ACE median fluorescence intensity (MFI) (C) and CD68+ myeloid cell presence in the lungs of WT and Marco-deficient male and female mice (C–F). Plasma sodium and potassium levels in male and female mice (G–J). Systolic, diastolic, and mean blood pressure measurements in male mice of the indicated genotypes (K–M). Data in (A), (C–M), were analysed by two-tailed unpaired Student’s t-test and are shown as average ± SEM. *p < 0.05, ***p < 0.001, ns = not significant.
Figure 5
A proposed model for macrophage-mediated regulation of lung Ace expression.
(A) Single-cell RNA-seq UMAP plot depicting the cell types present in the male murine lung. (B) Marker heatmap showing the top three gene markers for each cell cluster in (A). (C) A dot plot showing the gene expression levels of Marco and Ace in the different cell clusters of the male murine lung. (D) qPCR data showing the relative expression levels of Ace in co-coltures contraining HUVEC cells with Marco sufficient or deficient MPI macrophages. (E) A schematic, generated using BioRender, showing the working model by which Marco+ alveolar macrophages regulate aldosterone output from the adrenal gland. Data in (D) were analysed by two-tailed unpaired Student’s t-test and are shown as average ± SEM.
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Class A scavenger receptor MARCO negatively regulates Ace expression and aldosterone production
eLife 12:RP91318.
https://doi.org/10.7554/eLife.91318.3
