ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025
Aldosterone induces renal lymphangiogenesis through macrophage-lymphatic endothelial cell transformation and Inhibition by esaxerenone.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Esaxerenone attenuates renal injury by inhibiting NR3C2-mediated inflammatory and fibrotic pathways.Renal failure · 2026Article
- The crosstalk between lymphatic endothelial cells and immune cells in Physiological and Pathological conditions.Cellular and molecular life sciences : CMLS · 2026Review
- Esaxerenone Attenuates Aldosterone-Induced Renal Fibrosis by Suppressing Fibroblast-to-Lymphatic Endothelial-like Cell Transdifferentiation.International journal of molecular sciences · 2026Article
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11 authors.
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Abstract
OBJECTIVE AND
designInflammation plays a crucial role in the occurrence and development of renal fibrosis. Lymphatic vessels have emerged as new hotspots in the domain of inflammation. Recent studies have revealed that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms. However, the underlying mechanisms of macrophage transdifferentiation into lymphatic endothelial cells (LECs) are still poorly understood.
methodsIn vivo, thirty male Wistar rats were randomly divided into a sham group, an aldosterone group and an aldosterone + esaxerenone group. In vitro, Raw 264.7 cells and bone marrow-derived macrophages (BMDMs) were used. H&E, Masson, western blotting, immunohistochemistry, immunofluorescence, flow cytometry, and BMDM tube formation assays were used to assess renal fibrosis and lymphangiogenesis in a rat model of aldosterone-induced renal injury.
resultsIn this study, we observed pathological renal fibrosis and lymphangiogenesis in 12-week-old rats after aldosterone infusion. In addition, the treatment of rats with esaxerenone, a mineralocorticoid receptor blocker (MRB), significantly reduced renal lymphangiogenesis and fibrosis. Interestingly, we found that aldosterone can activate MR to stimulate macrophages to secrete vascular endothelial growth factor C (VEGF-C) and promote lymphatic angiogenesis.
conclusionsOur data suggest that renal fibrosis occurs in aldosterone-treated rats and that inflammation-induced macrophage transdifferentiation into LECs occurs during this process and that MRB attenuates renal fibrosis and lymphangiogenesis due to inflammatory injury.
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