phenotypic-characterization-macrophages-from-rat-kidney-flow

Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry

There is increasing evidence suggesting the important role of inflammation and, subsequently, macrophages in the development and progression of renal ...

Complutense University

We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory alterations in rat kidney by aldosterone + salt administration. The effects of treatment with spironolactone on above parameters were also analyzed. Male Wistar rats received aldosterone (1 mgkg-1d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg kg-1d-1). Systolic and diastolic blood pressures were elevated (p<0.05) in aldosterone + salt-treated rats. Relative kidney weight, collagen content, fibronectin, macrophage infiltrate, CTGF, Col I, MMP2, TNF-α, CD68, Arg2, and SGK-1 were increased (p<0.05) in aldosterone + salt-treated rats, being reduced by spironolactone (p<0.05). Increased iNOS and IFN-γ mRNA gene expression (M1 macrophage markers) was observed in aldosterone + salt rats, whereas no significant differences were observed in IL-10 and gene ArgI mRNA expression or ED2 protein content (M2 macrophage markers). All the observed changes were blocked with spironolactone treatment. Macrophage depletion with liposomal clodronate reduced macrophage influx and inflammatory M1 markers (INF-γ or iNOS), whereas interstitial fibrosis was only partially reduced after this intervention, in aldosterone plus salt-treated rats. In conclusion, aldosterone + salt administration mediates inflammatory M1 macrophage phenotype and increased fibrosis throughout mineralocorticoid receptors activation.

Aldosterone Induces Renal Fibrosis and Inflammatory M1-Macrophage Subtype via Mineralocorticoid Receptor in Rats.

Aldosterone plays a central role in the development of cardiac pathological states involving ion transport imbalances, especially sodium transport. We have previously demonstrated a cardioprotective effect of proanthocyanidins in aldosterone-treated rats. Our objective was to investigate for the first time the effect of proanthocyanidins on serum and glucocorticoid-regulated kinase 1 (SGK1), epithelial Na(+) channel (γ-ENaC), neuronal precursor cells expressed developmentally down-regulated 4-2 (Nedd4-2) and phosphoNedd4-2 protein expression in the hearts of aldosterone-treated rats. Male Wistar rats received aldosterone (1mg kg(-1)day(-1))+1% NaCl for 3weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5mg kg(-1)day(-1)). Hypertension and diastolic dysfunction induced by aldosterone were abolished by treatment with PRO80. Expression of fibrotic, inflammatory and oxidative mediators were increased by aldosterone-salt administration and blunted by PRO80. Antioxidant capacity was improved by PRO80. The up-regulated aldosterone mediator SGK1, ENaC and p-Nedd4-2/total Nedd4-2 ratio were blocked by PRO80. PRO80 blunted aldosterone-mineralocorticoid-mediated up-regulation of ENaC provides new mechanistic insight of the beneficial effect of proanthocyanidins preventing the cardiac alterations induced by aldosterone excess.

Article	Year
Aldosterone Induces Renal Fibrosis and Inflammatory M1-Macrophage Subtype via Mineralocorticoid Receptor in Rats. PloS one\| PubMed ID: 26730742	2016
Proanthocyanidins block aldosterone-dependent up-regulation of cardiac gamma ENaC and Nedd4-2 inactivation via SGK1. The Journal of nutritional biochemistry\| PubMed ID: 27592201	2016

Elena Olivares-Alvaro

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