Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels
Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (K<sub>Ca</sub&g...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/4/538 |
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| author | Marta Morotti Stefano Garofalo Germana Cocozza Fabrizio Antonangeli Valeria Bianconi Chiara Mozzetta Maria Egle De Stefano Riccardo Capitani Heike Wulff Cristina Limatola Myriam Catalano Francesca Grassi |
| author_facet | Marta Morotti Stefano Garofalo Germana Cocozza Fabrizio Antonangeli Valeria Bianconi Chiara Mozzetta Maria Egle De Stefano Riccardo Capitani Heike Wulff Cristina Limatola Myriam Catalano Francesca Grassi |
| author_sort | Marta Morotti |
| collection | DOAJ |
| description | Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (K<sub>Ca</sub>3.1) plays key roles in controlling both macrophage phenotype and fibroblast proliferation, two critical contributors to muscle damage. In this work, we demonstrate that pharmacological blockade of the channel in the <i>mdx</i> mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in muscles, with a concomitant reduction of muscle damage. As already observed with other treatments, no improvement in muscle performance was observed in vivo. In conclusion, this work supports the idea that K<sub>Ca</sub>3.1 channels play a contributing role in controlling damage-causing cells in DMD. A more complete understanding of their function could lead to the identification of novel therapeutic approaches. |
| first_indexed | 2024-03-09T04:30:11Z |
| format | Article |
| id | doaj.art-c150d023676543ebae690e664575e39d |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T04:30:11Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-c150d023676543ebae690e664575e39d2023-12-03T13:37:12ZengMDPI AGLife2075-17292022-04-0112453810.3390/life12040538Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 ChannelsMarta Morotti0Stefano Garofalo1Germana Cocozza2Fabrizio Antonangeli3Valeria Bianconi4Chiara Mozzetta5Maria Egle De Stefano6Riccardo Capitani7Heike Wulff8Cristina Limatola9Myriam Catalano10Francesca Grassi11Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, 86077 Pozzilli, ItalyInstitute of Molecular Biology and Pathology-National Research Council (CNR), Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, ItalyInstitute of Molecular Biology and Pathology-National Research Council (CNR), Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, ItalyInstitute of Molecular Biology and Pathology-National Research Council (CNR), Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pharmacology, University of California, Davis, CA 95616, USAIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, 86077 Pozzilli, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDuchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (K<sub>Ca</sub>3.1) plays key roles in controlling both macrophage phenotype and fibroblast proliferation, two critical contributors to muscle damage. In this work, we demonstrate that pharmacological blockade of the channel in the <i>mdx</i> mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in muscles, with a concomitant reduction of muscle damage. As already observed with other treatments, no improvement in muscle performance was observed in vivo. In conclusion, this work supports the idea that K<sub>Ca</sub>3.1 channels play a contributing role in controlling damage-causing cells in DMD. A more complete understanding of their function could lead to the identification of novel therapeutic approaches.https://www.mdpi.com/2075-1729/12/4/538Duchenne muscular dystrophymacrophagesfibroblastsfibrosisKcnn4K<sub>Ca</sub>3.1 |
| spellingShingle | Marta Morotti Stefano Garofalo Germana Cocozza Fabrizio Antonangeli Valeria Bianconi Chiara Mozzetta Maria Egle De Stefano Riccardo Capitani Heike Wulff Cristina Limatola Myriam Catalano Francesca Grassi Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels Life Duchenne muscular dystrophy macrophages fibroblasts fibrosis Kcnn4 K<sub>Ca</sub>3.1 |
| title | Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels |
| title_full | Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels |
| title_fullStr | Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels |
| title_full_unstemmed | Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels |
| title_short | Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca<sup>2+</sup>-Activated K<sub>Ca</sub>3.1 Channels |
| title_sort | muscle damage in dystrophic mdx mice is influenced by the activity of ca sup 2 sup activated k sub ca sub 3 1 channels |
| topic | Duchenne muscular dystrophy macrophages fibroblasts fibrosis Kcnn4 K<sub>Ca</sub>3.1 |
| url | https://www.mdpi.com/2075-1729/12/4/538 |
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