Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystro- phin 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 (KCa3.1) 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 mdx mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in mus- cles, 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 KCa3.1 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 therapeu- tic approaches.

Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels / Morotti, Marta; Garofalo, Stefano; Cocozza, Germana; Antonangeli, Fabrizio; Bianconi, Valeria; Mozzetta, Chiara; De Stefano, Maria Egle; Capitani, Riccardo; Wulff, Heike; Limatola, Cristina; Catalano, Myriam; Grassi, Francesca. - In: LIFE. - ISSN 2075-1729. - 12:4(2022), p. 538. [10.3390/life12040538]

Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels

Morotti, Marta
Primo
;
Garofalo, Stefano;Cocozza, Germana;Antonangeli, Fabrizio;Bianconi, Valeria;Mozzetta, Chiara;De Stefano, Maria Egle;Capitani, Riccardo;Limatola, Cristina;Catalano, Myriam;Grassi, Francesca
Ultimo
Funding Acquisition
2022

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystro- phin 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 (KCa3.1) 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 mdx mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in mus- cles, 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 KCa3.1 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 therapeu- tic approaches.
2022
Duchenne muscular dystrophy; macrophages; fibroblasts; fibrosis; Kcnn4; KCa3.1; grip strength; hanging time; neuromuscular junction; fiber size
01 Pubblicazione su rivista::01a Articolo in rivista
Muscle Damage in Dystrophic mdx Mice Is Influenced by the Activity of Ca2+-Activated KCa3.1 Channels / Morotti, Marta; Garofalo, Stefano; Cocozza, Germana; Antonangeli, Fabrizio; Bianconi, Valeria; Mozzetta, Chiara; De Stefano, Maria Egle; Capitani, Riccardo; Wulff, Heike; Limatola, Cristina; Catalano, Myriam; Grassi, Francesca. - In: LIFE. - ISSN 2075-1729. - 12:4(2022), p. 538. [10.3390/life12040538]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1628239
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