Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor

J Invest Dermatol. 1996 Sep;107(3):404-11. doi: 10.1111/1523-1747.ep12363389.


Connective tissue growth factor (CTGF) is a 36-to 38-kDa peptide that is selectively induced by transforming growth factor-beta (TGF-beta) in fibroblastic cell types. We compared the biologic activities of CTGF with TGF-beta on fibroblasts in culture and in animal models of fibroplasia. CTGF was active as a mitogen in monolayer cultures of normal rat kidney fibroblasts. CTGF did not stimulate anchorage-independent growth of NRK fibroblasts, however, or inhibit the growth of mink lung epithelial cells, distinguishing CTGF's growth-regulatory activities from those of TGF-beta. In NRK fibroblasts, both TGF-beta and CTGF significantly increased the transcripts encoding alpha 1 type I collagen, alpha 5 integrin, and fibronectin. Stimulation of type I collagen and fibronectin protein synthesis by TGF-beta and CTGF was confirmed by pulse labeling of cells with [35S]methionine. Subcutaneous injection of TGF-beta and CTGF into neonatal NIH Swiss mice resulted in a large stimulation of granulation tissue and fibrosis at the site of injection. In situ hybridization studies revealed that TGF-beta injection induced high levels of CTGF mRNA in the dermal fibroblasts at the injection site, demonstrating that TGF-beta can induce the expression of CTGF in connective tissue cells in vivo. No CTGF transcripts were detected in the epidermal cells in either control or TGF-beta-injected skin or in fibroblasts in control (saline-injected) skin. These results demonstrate that, like TGF-beta, CTGF can induce connective tissue cell proliferation and extracellular matrix synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Connective Tissue Growth Factor
  • Epithelial Cells
  • Epithelium / drug effects
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Granulation Tissue / drug effects*
  • Granulation Tissue / growth & development
  • Growth Inhibitors / pharmacology
  • Growth Substances / genetics
  • Growth Substances / pharmacology*
  • Immediate-Early Proteins*
  • Intercellular Signaling Peptides and Proteins*
  • Mice
  • Mice, Inbred Strains
  • Mitogens / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Proteins
  • Skin / drug effects
  • Skin / pathology
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / pharmacology


  • CCN2 protein, mouse
  • CCN2 protein, rat
  • Extracellular Matrix Proteins
  • Growth Inhibitors
  • Growth Substances
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Mitogens
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor