Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy

J Neurol Sci. 2008 Apr 15;267(1-2):48-56. doi: 10.1016/j.jns.2007.09.043. Epub 2007 Nov 9.


The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-beta1 (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Biopsy
  • Child
  • Child, Preschool
  • Connective Tissue / metabolism*
  • Connective Tissue / pathology*
  • Connective Tissue / physiopathology
  • Connective Tissue Growth Factor
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis / genetics
  • Fibrosis / metabolism
  • Fibrosis / physiopathology
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Immunohistochemistry
  • Infant
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism*
  • Muscular Dystrophies / physiopathology
  • Paracrine Communication / physiology
  • RNA, Messenger / metabolism
  • Regeneration / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / metabolism


  • Biomarkers
  • CCN2 protein, human
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor