Extracellular matrix (ECM) proteins, including collagen and growth factors, are greatly increased in tissue fibrosis and mainly secreted by fibroblasts. We previously demonstrated that muscle-derived fibroblasts from Duchenne muscular dystrophy (DMD) patients have a profibrotic phenotype, that includes significantly reduced expression of tissue inhibitor of metalloprotease 3 (TIMP-3) compared to control. Since TIMP-3 induces apoptosis in various cell types, we hypothesized increased resistance of DMD fibroblasts to apoptosis. To address this, we evaluated apoptotic nuclei, caspase 3, caspase 3 substrate expression, and migration and adhesion properties of muscle-derived fibroblasts, after applying different apoptosis-inducing treatments. We found that DMD fibroblasts were less susceptible to cell death, more adhesive, and had greater tendency to migrate than control fibroblasts findings further supported by alterations in FAK and ERK/MAPK expression. Resistance to apoptosis and greater adhesion are likely to contribute to muscle fibrosis so a pharmacological treatment that targets dysregulated pathways involved in cell detachment apoptosis (anoikis) may limit the progressive fibrotic remodeling characteristic of DMD. (C) 2011 Elsevier Inc. All rights reserved

Zanotti, S., Gibertini, S., Bragato, C., Mantegazza, R., Morandi, L., Mora, M. (2011). Fibroblasts from the muscles of Duchenne muscular dystrophy patients are resistant to cell detachment apoptosis. EXPERIMENTAL CELL RESEARCH, 317(17), 2536-2547 [10.1016/j.yexcr.2011.08.004].

Fibroblasts from the muscles of Duchenne muscular dystrophy patients are resistant to cell detachment apoptosis

Zanotti, S;Gibertini, S;Bragato, C;
2011

Abstract

Extracellular matrix (ECM) proteins, including collagen and growth factors, are greatly increased in tissue fibrosis and mainly secreted by fibroblasts. We previously demonstrated that muscle-derived fibroblasts from Duchenne muscular dystrophy (DMD) patients have a profibrotic phenotype, that includes significantly reduced expression of tissue inhibitor of metalloprotease 3 (TIMP-3) compared to control. Since TIMP-3 induces apoptosis in various cell types, we hypothesized increased resistance of DMD fibroblasts to apoptosis. To address this, we evaluated apoptotic nuclei, caspase 3, caspase 3 substrate expression, and migration and adhesion properties of muscle-derived fibroblasts, after applying different apoptosis-inducing treatments. We found that DMD fibroblasts were less susceptible to cell death, more adhesive, and had greater tendency to migrate than control fibroblasts findings further supported by alterations in FAK and ERK/MAPK expression. Resistance to apoptosis and greater adhesion are likely to contribute to muscle fibrosis so a pharmacological treatment that targets dysregulated pathways involved in cell detachment apoptosis (anoikis) may limit the progressive fibrotic remodeling characteristic of DMD. (C) 2011 Elsevier Inc. All rights reserved
Articolo in rivista - Articolo scientifico
Apoptosis; Anoikis; Fibrosis; TIMP-3; Cell adhesion; Cells, Cultured; Child; Child, Preschool; Fibroblasts; Humans; Infant; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Apoptosis
English
2011
317
17
2536
2547
none
Zanotti, S., Gibertini, S., Bragato, C., Mantegazza, R., Morandi, L., Mora, M. (2011). Fibroblasts from the muscles of Duchenne muscular dystrophy patients are resistant to cell detachment apoptosis. EXPERIMENTAL CELL RESEARCH, 317(17), 2536-2547 [10.1016/j.yexcr.2011.08.004].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/204770
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