期刊
JOURNAL OF CELL COMMUNICATION AND SIGNALING
卷 12, 期 1, 页码 413-421出版社
SPRINGER
DOI: 10.1007/s12079-017-0409-3
关键词
CTGF/CCN2; Muscular dystrophy; Fibrosis; Inflammation; Necrotic-regenerative focus
类别
资金
- Fondecyt [1150106, 3140323]
- [CARE-PFB-12/2007]
Connective tissue growth factor (CTGF/CCN2) has strong inflammatory and profibrotic activities. Its expression is enhanced in skeletal muscular dystrophies such as Duchenne muscular dystrophy (DMD), a myopathy characterized by exacerbated inflammation and fibrosis. In dystrophic tissue, necrotic-regenerative foci, myofibroblasts, newly-regenerated muscle fibers and necrosis all occur simultaneously. To determine if CCN2 is involved in the appearance of the foci, we studied their presence and characteristics in mdx mice (DMD mouse model) compared to mdx mice hemizygous for CCN2 (mdx-Ccn2+/-). We used laser capture microdissection followed by gene expression and immunofluorescence analyses to investigate fibrotic, inflammation and regeneration markers in damaged and nondamaged areas in mdx and mdx-Ccn2+/-skeletal muscle. Mdx mice foci express elevated mRNAs levels of transforming growth factor type beta, collagen, fibronectin, the myofribroblast marker alpha-SMA, and the myogenic transcription factor myogenin. Mdx foci also show elevated levels of MCP-1 and CD-68 positive cells, indicating that CCN2 could be inducing an inflammatory response. We found a significant reduction in the number of foci in mdx-Ccn2+/-mice muscle. Fibrotic and inflammatory markers were also decreased in these foci. We did not observe any difference in Pax7 mRNA levels, a marker for satellite cells, in mdx mice compared to mdx-Ccn2+/mice. Thus, CCN2 appears to be involved in the fibrotic response as well as in the inflammatory response in the dystrophic skeletal muscle.
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