| Author | Pons, Andrea Henriques | |
| Author | Yu, Qing | |
| Author | Rayavarapu, Sree | |
| Author | Cohen, Tatiana V | |
| Author | Ampong, Beryl | |
| Author | Cha, Hee Jae | |
| Author | Jahnke, Vanessa | |
| Author | Van der Meulen, Jack | |
| Author | Wang, Daqing | |
| Author | Jiang, Weiwen | |
| Author | Kandimalla, Ekambar R | |
| Author | Agrawal, Sudhir | |
| Author | Spurney, Christopher F | |
| Author | Nagaraju, Kanneboyina | |
| Access date | 2015-06-01T19:34:24Z | |
| Available date | 2015-06-01T19:34:24Z | |
| Document date | 2014 | |
| Citation | 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 | |
| Language | eng | pt_BR |
| Publisher | Oxford University Press | pt_BR |
| Rights | open access | |
| Title | Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle | pt_BR |
| Type | Article | |
| DOI | 10.1093/hmg/ddt656 | pt_BR |
| Abstract | 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 |
| Affilliation | 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 |
| Affilliation | Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USA | pt_BR |
| Affilliation | 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 |
| Affilliation | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA. | pt_BR |
| Affilliation | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
| Affilliation | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
| Affilliation | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
| Affilliation | Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA | pt_BR |
| Affilliation | Idera Pharmaceuticals, Inc.. Cambridge, MA, USA. | pt_BR |
| Affilliation | Idera Pharmaceuticals, Inc., Cambridge, MA, USA. | pt_BR |
| Affilliation | Idera Pharmaceuticals, Inc., Cambridge, MA, USA. | pt_BR |
| Affilliation | Idera Pharmaceuticals, Inc., Cambridge, MA, USA. | pt_BR |
| Affilliation | Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USA | pt_BR |
| Affilliation | Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USA | pt_BR |
| Subject | Heart muscle | pt_BR |
| Subject | Dystrophin-deficient skeletal | pt_BR |
| Subject | Duchenne muscular dystrophy (DMD) | pt_BR |
| Subject | Toll-like receptors (TLRs) | pt_BR |
