Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor
Chronic inflammation is a feature of Duchenne muscular dystrophy (DMD), a degenerative striated muscle disease. Mineralocorticoid receptor (MR) antagonists (MRAs) have demonstrated clinical benefit on later onset DMD cardiomyopathy, and preclinical studies in mouse models have demonstrated efficacy...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-12-01
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| Series: | Endocrine and Metabolic Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666396125000524 |
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| author | Jeovanna Lowe Arden B. Piepho Chetan K. Gomatam Peyton Debell Megan N. Ballinger Jill A. Rafael-Fortney |
| author_facet | Jeovanna Lowe Arden B. Piepho Chetan K. Gomatam Peyton Debell Megan N. Ballinger Jill A. Rafael-Fortney |
| author_sort | Jeovanna Lowe |
| collection | DOAJ |
| description | Chronic inflammation is a feature of Duchenne muscular dystrophy (DMD), a degenerative striated muscle disease. Mineralocorticoid receptor (MR) antagonists (MRAs) have demonstrated clinical benefit on later onset DMD cardiomyopathy, and preclinical studies in mouse models have demonstrated efficacy on multiple steps of skeletal muscle pathology. MRA treatment of the mdx mouse model reduces pro-inflammatory gene expression from skeletal muscle myeloid immune cells and represses muscle cytokine signaling and fibrosis. Myofiber-specific knockout of MR in mdx mice improves muscle force and reduces fibrosis, but inflammation in this model had not been investigated. In this study we investigated muscle inflammation at the cellular level using flow cytometry and at the protein signaling level using an unbiased cytokine assay. Numbers and proportions of myeloid cells were the same in mdx mice and those lacking myofiber MR, similar to the absence of cell type differences previously observed with either MRA treatment or myeloid MR knockout. MRA treatment, but not myofiber MR deletion alone, led to reductions in numerous cytokines and chemokines also previously observed in mdx mice. These data suggest that the beneficial reduction of inflammatory signaling from MRAs is largely independent of myofiber MR and occurs through another mechanism. |
| format | Article |
| id | doaj-art-415c4b43ea634c818d6c92409feb755f |
| institution | DOAJ |
| issn | 2666-3961 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Endocrine and Metabolic Science |
| spelling | doaj-art-415c4b43ea634c818d6c92409feb755f2025-08-20T02:57:30ZengElsevierEndocrine and Metabolic Science2666-39612025-12-011910026610.1016/j.endmts.2025.100266Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptorJeovanna Lowe0Arden B. Piepho1Chetan K. Gomatam2Peyton Debell3Megan N. Ballinger4Jill A. Rafael-Fortney5Department of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USADivision of Pulmonary, Critical Care and Sleep Medicine, Dept. of Internal Medicine, Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH, USADepartment of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA; Corresponding author at: Department of Physiology & Cell Biology, College of Medicine, The Ohio State University, 390 Biomedical Research Tower, 460 W. 12th Avenue, Columbus, OH 43210, USA.Chronic inflammation is a feature of Duchenne muscular dystrophy (DMD), a degenerative striated muscle disease. Mineralocorticoid receptor (MR) antagonists (MRAs) have demonstrated clinical benefit on later onset DMD cardiomyopathy, and preclinical studies in mouse models have demonstrated efficacy on multiple steps of skeletal muscle pathology. MRA treatment of the mdx mouse model reduces pro-inflammatory gene expression from skeletal muscle myeloid immune cells and represses muscle cytokine signaling and fibrosis. Myofiber-specific knockout of MR in mdx mice improves muscle force and reduces fibrosis, but inflammation in this model had not been investigated. In this study we investigated muscle inflammation at the cellular level using flow cytometry and at the protein signaling level using an unbiased cytokine assay. Numbers and proportions of myeloid cells were the same in mdx mice and those lacking myofiber MR, similar to the absence of cell type differences previously observed with either MRA treatment or myeloid MR knockout. MRA treatment, but not myofiber MR deletion alone, led to reductions in numerous cytokines and chemokines also previously observed in mdx mice. These data suggest that the beneficial reduction of inflammatory signaling from MRAs is largely independent of myofiber MR and occurs through another mechanism.http://www.sciencedirect.com/science/article/pii/S2666396125000524InflammationMuscular dystrophymdxMineralocorticoid receptorMyeloid |
| spellingShingle | Jeovanna Lowe Arden B. Piepho Chetan K. Gomatam Peyton Debell Megan N. Ballinger Jill A. Rafael-Fortney Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor Endocrine and Metabolic Science Inflammation Muscular dystrophy mdx Mineralocorticoid receptor Myeloid |
| title | Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor |
| title_full | Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor |
| title_fullStr | Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor |
| title_full_unstemmed | Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor |
| title_short | Mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor |
| title_sort | mineralocorticoid receptor antagonists reduce inflammatory signaling independent of myofiber mineralocorticoid receptor |
| topic | Inflammation Muscular dystrophy mdx Mineralocorticoid receptor Myeloid |
| url | http://www.sciencedirect.com/science/article/pii/S2666396125000524 |
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