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Autor | Pons, Andrea Henriques | |
Autor | Yu, Qing | |
Autor | Rayavarapu, Sree | |
Autor | Cohen, Tatiana V | |
Autor | Ampong, Beryl | |
Autor | Cha, Hee Jae | |
Autor | Jahnke, Vanessa | |
Autor | Van der Meulen, Jack | |
Autor | Wang, Daqing | |
Autor | Jiang, Weiwen | |
Autor | Kandimalla, Ekambar R | |
Autor | Agrawal, Sudhir | |
Autor | Spurney, Christopher F | |
Autor | Nagaraju, Kanneboyina | |
Fecha de acceso | 2015-06-01T19:34:24Z | |
Fecha de disponibilización | 2015-06-01T19:34:24Z | |
Fecha de publicación | 2014 | pt_BR |
Referencia | PONS, Andrea Henriques et al. Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. Human Molecular Genetics, v.23, n.10, p. 2604-2607, 2014. | pt_BR |
ISSN | 1460-2083 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/10615 | |
Idioma | eng | pt_BR |
Editor | Oxford University Press | pt_BR |
Derechos de autor | open access | pt_BR |
Título | Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle | pt_BR |
Tipo del documento | Article | pt_BR |
DOI | 10.1093/hmg/ddt656 | pt_BR |
Resumen en Inglés | Although the cause of Duchenne muscular dystrophy (DMD) is known, the specific factors that initiate and perpetuate disease progression are not well understood.We hypothesized that leaky dystrophin-deficient skeletal muscle releases endogenous danger signals (TLR ligands), which bind to Toll-like receptors (TLRs) on muscle andimmunecellsand activate downstreamprocesses that facilitate degeneration andregeneration in dystrophic skeletal muscle. Here, we demonstrate that dystrophin-deficient mousemuscle cells show increased expression of several cell-surface and endosomal TLRs. In vitro screening identified ssRNA as a relevant endogenous TLR7 ligand. TLR7 activation led to myd88-dependent production of pro-inflammatory cytokines in dystrophindeficient muscle cells, and cause significant degeneration/regeneration in vivo in mdx mouse muscle. Also, knockout of the central TLR adaptor protein, myd88 in mdx mice significantly improved skeletal and cardiac muscle function. Likewise, proof-of-concept experiments showed that treating young mdx mice with a TLR7/9 antagonist significantly reduced skeletal muscle inflammation and increased muscle force, suggesting that blocking this pathway may have therapeutic potential for DMD. | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Afiliación | Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USA | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA / The George Washington University. Department of Integrative Systems Biology. Washington, DC, USA. | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA. | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
Afiliación | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
Afiliación | Idera Pharmaceuticals, Inc.. Cambridge, MA, USA. | pt_BR |
Afiliación | Idera Pharmaceuticals, Inc., Cambridge, MA, USA. | pt_BR |
Afiliación | Idera Pharmaceuticals, Inc., Cambridge, MA, USA. | pt_BR |
Afiliación | Idera Pharmaceuticals, Inc., Cambridge, MA, USA. | pt_BR |
Afiliación | Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USA | pt_BR |
Afiliación | Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USA | pt_BR |
Palavras clave en Inglês | Heart muscle | pt_BR |
Palavras clave en Inglês | Dystrophin-deficient skeletal | pt_BR |
Palavras clave en Inglês | Duchenne muscular dystrophy (DMD) | pt_BR |
Palavras clave en Inglês | Toll-like receptors (TLRs) | pt_BR |
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