Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6986
Aldosterone Induces Renal Fibrosis and Inflammatory M1-Macrophage Subtype via Mineralocorticoid Receptor in Rats
Martín-Fernández, Beatriz | Rubio-Navarro, Alfonso | Cortegano, Isabel ISCIII | Ballesteros, Sandra | Alia, Mario ISCIII | Cannata-Ortiz, Pablo | Olivares-Álvaro, Elena | Egido, Jesús | Andres, Belen de ISCIII | Gaspar, Maria Luisa ISCIII | de Las Heras, Natalia | Lahera, Vicente | Moreno, Juan Antonio
PLoS One. 2016 Jan 5;11(1):e0145946
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 | Animals | Fibrosis | Inflammation | Kidney | Kidney Diseases | Macrophages | Male | Mineralocorticoid Receptor Antagonists | Rats | Rats, Wistar | Receptors, Mineralocorticoid | Sodium Chloride | Spironolactone
Files in this item
- AldosteroneInducesRenalFibrosi ...