کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2130930 | 1086611 | 2011 | 12 صفحه PDF | دانلود رایگان |
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.
► Muscle-derived DMD fibroblasts have a pro-fibrotic phenotype.
► We now find lower cell detachment apoptosis (anoikis) than in control fibroblasts.
► DMD fibroblasts are also more adhesive and have greater tendency to migrate.
► Thus, they are likely to contribute to the fibrotic remodeling of DMD muscle.
► A drug targeting dysregulated anoikis pathways could limit fibrosis in DMD.
Journal: Experimental Cell Research - Volume 317, Issue 17, 15 October 2011, Pages 2536–2547