Role of thrombospondin 1 in macrophage inflammation in dysferlin myopathy

Noemí De Luna, Eduard Gallardo, Corinne Sonnet, Bénédicte Chazaud, Raúl Dominguez-Perles, Xavier Suarez-Calvet, Romain K. Gherardi, Isabel Illa

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28 Citations (Scopus)


Muscle inflammation can be a prominent feature in several muscular dystrophies. In dysferlin myopathy, it is mainly composed of macrophages. To understand the origin of inflammation in dysferlin-deficient muscle, we analyzed soluble factors involved in monocyte chemotaxis released by myoblasts and myotubes from control and dysferlinopathy patients using a transwell system. Dysferlin-deficient myotubes released more soluble factors involved in monocyte chemotaxis compared with controls (p < 0.001). Messenger RNA microarray analysis showed a 3.2-fold increase of thrombospondin 1 (TSP-1) expression in dysferlin-deficient myotubes. Retrotranscriptasepolymerase chain reaction analysis, ELISA, and immunohistochemistry confirmed these results. Dysferlin mRNA knockdown with short-interfering RNA in normal myogenic cells resulted in TSP-1 mRNA upregulation and increased chemotaxis. Furthermore, monocyte chemotaxis was decreased when TSP-1 was blocked by specific antibodies. In muscle biopsies from dysferlinopathy patients, TSP-1 expression was increased in muscle fibers but not in biopsies of patientswith other myopathies with inflammation; TSP-1 was seen in some macrophages in all samples analyzed. Taken together, the data demonstrate that dysferlin-deficient muscle upregulates TSP-1 in vivoand in vitro and indicate that endogenous chemotactic factors arecrucial to the sustained inflammatory process observed in dysferlinopathies. © 2010 by the American Association of Neuropathologists, Inc.
Original languageEnglish
Pages (from-to)643-653
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
Publication statusPublished - 1 Jun 2010


  • Chemotaxis
  • Dysferlin
  • Inflammation
  • Macrophages
  • Myopathy
  • Myotubes
  • Thrombospondin 1


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