Dysregulated Intracellular Signaling and Inflammatory Gene Expression During Initial Disease Onset in Duchenne Muscular Dystrophy

被引:65
作者
Evans, Nicholas P. [1 ]
Misyak, Sarah A. [1 ]
Robertson, John L. [2 ]
Bassaganya-Riera, Josep [3 ]
Grange, Robert W. [1 ]
机构
[1] Virginia Polytech Inst & State Univ, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA
[2] Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA
[3] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA
关键词
Duchenne Muscular Dystrophy; mdx; Intracellular Signaling; Transcription Factors; Inflammatory Gene Expression; Cytokines; FACTOR-KAPPA-B; EXTENSOR DIGITORUM LONGUS; SKELETAL-MUSCLE MYOPATHY; MESSENGER-RNA EXPRESSION; ACTIVATED T-CELLS; MDX MOUSE; NUCLEAR-FACTOR; GREEN TEA; GLYCOPROTEIN COMPLEX; TIME-COURSE;
D O I
10.1097/PHM.0b013e3181a5a24f
中图分类号
R49 [康复医学];
学科分类号
100232 [康复医学];
摘要
Duchenne muscular dystrophy is a debilitating genetic disorder characterized by severe muscle wasting and early death in affected boys. The primary cause of this disease is mutations in the dystrophin gene that result in the absence of the protein dystrophin and the associated dystrophin-glycoprotein complex in the plasma membrane of muscle fibers. In normal muscle, this complex forms a link between the extracellular matrix and the cytoskeleton that is thought to protect muscle fibers from contraction-induced membrane lesions and to regulate cell signaling cascades. Although the primary defect is known, the mechanisms that initiate disease onset have not been characterized. Data collected during early maturation suggest that inflammatory and immune responses are key contributors to disease pathogenesis and may be initiated by aberrant signaling in dystrophic muscle. However, detailed time course studies of the inflammatory and immune processes are incomplete and need to be characterized further to understand the disease progression. The purposes of this review are to examine the possibility that initial disease onset in dystrophin-deficient muscle results from aberrant inflammatory signaling pathways and to highlight the potential clinical relevance of targeting these pathways to treat Duchenne muscular dystrophy.
引用
收藏
页码:502 / 522
页数:21
相关论文
共 130 条
[21]
A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IκB kinase activation and IL-8 gene expression in respiratory epithelium [J].
Chen, PC ;
Wheeler, DS ;
Malhotra, V ;
Odoms, K ;
Denenberg, AG ;
Wong, HR .
INFLAMMATION, 2002, 26 (05) :233-241
[22]
Early onset of inflammation and later involvement of TGFβ in Duchenne muscular dystrophy [J].
Chen, YW ;
Nagaraju, K ;
Bakay, M ;
McIntyre, O ;
Rawat, R ;
Shi, R ;
Hoffman, EP .
NEUROLOGY, 2005, 65 (06) :826-834
[23]
A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type [J].
Chin, ER ;
Olson, EN ;
Richardson, JA ;
Yano, Q ;
Humphries, C ;
Shelton, JM ;
Wu, H ;
Zhu, WG ;
Bassel-Duby, R ;
Williams, RS .
GENES & DEVELOPMENT, 1998, 12 (16) :2499-2509
[24]
Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies [J].
Collins, CA ;
Morgan, JE .
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2003, 84 (04) :165-172
[25]
High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy [J].
Connolly, AM ;
Schierbecker, J ;
Renna, R ;
Florence, J .
NEUROMUSCULAR DISORDERS, 2002, 12 (10) :917-925
[26]
THE MDX MOUSE SKELETAL-MUSCLE MYOPATHY .2. CONTRACTILE PROPERTIES [J].
COULTON, GR ;
CURTIN, NA ;
MORGAN, JE ;
PARTRIDGE, TA .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1988, 14 (04) :299-314
[27]
THE MDX MOUSE SKELETAL-MUSCLE MYOPATHY .1. A HISTOLOGICAL, MORPHOMETRIC AND BIOCHEMICAL INVESTIGATION [J].
COULTON, GR ;
MORGAN, JE ;
PARTRIDGE, TA ;
SLOPER, JC .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1988, 14 (01) :53-70
[28]
[29]
MUSCLE DEVELOPMENT IN MDX MUTANT MICE [J].
DANGAIN, J ;
VRBOVA, G .
MUSCLE & NERVE, 1984, 7 (09) :700-704
[30]
TRANSCRIPTIONAL REGULATION BY MAP KINASES [J].
DAVIS, RJ .
MOLECULAR REPRODUCTION AND DEVELOPMENT, 1995, 42 (04) :459-467