Connective tissue growth factor (CTGF) is a member of the recently describe
d CCN gene family which contains CTGF itself, cyr61, nov, elm1, Cop1, and W
ISP-3. CTGF is transcriptionally activated by several factors although its
stimulation by transforming growth factor beta (TGF-beta) has attracted con
siderable attention. CTGF acts to promote fibroblast proliferation, migrati
on, adhesion, and extracellular matrix formation, and its overproduction is
proposed to play a major role in pathways that lead to fibrosis, especiall
y those that are TGF-beta-dependent. This includes fibrosis of major organs
, fibroproliferative diseases, and scarring. CTGF also appears to play a ro
le in the extracellular matrix remodeling that occurs in normal physiologic
al processes such as embryogenesis, implantation, and wound healing. Howeve
r, recent advances have shown that CTGF is involved in diverse autocrine or
paracrine actions in several other cell types such as vascular endothelial
cells, epithelial cells, neuronal cells, vascular smooth muscle cells, and
cells of supportive skeletal tissues. Moreover, in some circumstances CTGF
has negative effects on cell growth in that it can be antimitotic and apop
totic. In light of these discoveries, CTGF has been implicated in a diverse
variety of processes that include neovascularization, transdifferentiation
, neuronal scarring, atherosclerosis, cartilage differentiation, and endoch
ondral ossification. CTGF has thus emerged as a potential important effecto
r molecule in both physiological and pathological processes and has provide
d a new target for therapeutic intervention in fibrotic diseases. (C) 2000
Academic Press.