Individual domains of connective tissue growth factor regulate fibroblast proliferation and myofibroblast differentiation.
All members of the Ctgf, Cyr61, and Nov (CCN) family share a high degree of sequence homology and conservation of structural motifs and domains. Here, we present data about a structure function analysis of connective tissue growth factor (CTGF), a prototypic member of the CCN family, which has been shown to be a downstream mediator of transforming growth factor-beta activities on fibroblasts. Our findings demonstrate the two domains of CTGF function to mediate two distinct biological effects. The N-terminal domain of CTGF mediates myofibroblast differentiation and collagen synthesis. The C-terminal domain of CTGF mediates fibroblast proliferation. These data provide a molecular basis for the divergence of CTGF actions on connective tissue cell types and suggest a model for functional analysis of all of the CCN family gene products.
Grotendorst
Gary R
GR
Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, S.E, Albuquerque, NM 87108, USA. ggrotend@lrri.org
Duncan
Matthew R
MR
D000818:Animals; D001665:Binding Sites; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D003239:Connective Tissue Cells; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000166:cytology*; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000502:physiology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000502:physiology*; D007668:Kidney; D032342:Muscle Cells / Q000166:cytology*; D055514:Nephroblastoma Overexpressed Protein; D051381:Rats; D011994:Recombinant Proteins; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000378:metabolism; D019700:Thrombospondin 1 / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000502:physiology
D019485:Bone Morphogenetic Proteins; C526317:CCN2 protein, human; C526316:CCN2 protein, rat; C526319:CCN3 protein, human; D006001:Glycoconjugates; D017874:Immediate-Early Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D011994:Recombinant Proteins; D013002:Somatomedins; D013431:Sulfates; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D003094:Collagen