Individual domains of connective tissue growth factor regulate fibroblast proliferation and myofibroblast differentiation

Abstract

ABSTRACT 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‐β 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, G. R., Duncan, M. R. Individual domains of connective tissue growth factor regulate fibroblast proliferation and myofibroblast differentiation.—Grotendorst, G. R., Duncan, M. R. Individual domains of connective tissue growth factor regulate fibroblast proliferation and myofibroblast differentiation. FASEB J . 19, 729–738 (2005)