title: Aldosterone Induces Renal Fibrosis and Inflammatory M1-Macrophage Subtype via Mineralocorticoid Receptor in Rats.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín-Fernández
authors.affiliation: Renal, Vascular and Diabetes Research Lab, IIS-Fundación Jiménez Díaz, Autonoma University (UAM), 28040, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rubio-Navarro
authors.affiliation: Department of Immunology, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cortegano
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ballesteros
authors.affiliation: Department of Immunology, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220, Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Alía
authors.affiliation: Department of Pathology, IIS-Fundación Jiménez Díaz, Autonoma University (UAM), 28040, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cannata-Ortiz
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Olivares-Álvaro
authors.affiliation: Renal, Vascular and Diabetes Research Lab, IIS-Fundación Jiménez Díaz, Autonoma University (UAM), 28040, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Department of Immunology, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: de Andrés
authors.affiliation: Department of Immunology, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28220, Madrid, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Gaspar
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: de Las Heras
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.affiliation: Renal, Vascular and Diabetes Research Lab, IIS-Fundación Jiménez Díaz, Autonoma University (UAM), 28040, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D005355:Fibrosis; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000276:immunology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000276:immunology*; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone