Journal of Cell Communication and Signaling

, Volume 12, Issue 1, pp 413–421 | Cite as

The pro-fibrotic connective tissue growth factor (CTGF/CCN2) correlates with the number of necrotic-regenerative foci in dystrophic muscle

  • María Gabriela Morales
  • María José Acuña
  • Daniel Cabrera
  • Roel Goldschmeding
  • Enrique BrandanEmail author
Research Article


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 non-damaged 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 α-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.


CTGF/CCN2 Muscular dystrophy Fibrosis Inflammation Necrotic-regenerative focus 



α-smooth muscle actin


Connective Tissue Growth Factor


Duchenne muscular dystrophy


Extracellular matrix


Hypoxia inducible factor- 1α


Laser capture microdissection


Monocyte chemoattractant protein-1


Transforming growth factor type-β



The authors are grateful to Victor Troncoso, Darling Vera and Lina Correa for technical support. This study received financial support from Fondecyt grant 1150106, the CARE-PFB-12/2007 grant and Fondecyt grant 3140323.


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Copyright information

© The International CCN Society 2017

Authors and Affiliations

  1. 1.Centro de Envejecimiento y Regeneración, CARE Chile UC y Departamento de Biología Celular y Molecular, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  2. 2.Departamento de Ciencias Químicas y Biológicas, Facultad de SaludSantiagoChile
  3. 3.Department of PathologyUniversity Medical Center UtrechtUtrechtNetherlands

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