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

S. Zanotti, S. Gibertini, C. Bragato, R. Mantegazza, L. Morandi, M. Mora

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2536-2547
Number of pages12
JournalExperimental Cell Research
Volume317
Issue number17
DOIs
Publication statusPublished - Oct 15 2011

Keywords

  • Anoikis
  • Apoptosis
  • Cell adhesion
  • Fibrosis
  • TIMP-3

ASJC Scopus subject areas

  • Cell Biology

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