Background: Connective tissue growth factor (CTGF) belongs to a family of f
actors that regulate fibrogenesis and wound healing. While the significance
of transforming growth factor beta (TGF-beta) in liver fibrosis is well es
tablished, the role of CTGF in fibrosing hepatopathy is still unknown. Meth
ods: CTGF was analyzed in 10 normal and in 16 cirrhotic liver tissue sample
s. Northern blot analysis was used to examine the concomitant expression of
CTGF and TGF-PL mRNAs, and the cellular localization of CTGF mRNA was stud
ied by in situ hybridization. For identification of myofibroblasts and acti
vated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) immunoh
istochemistry was used. Results: Northern blot analysis showed 6.5-fold enh
anced expression of CTGF mRNA and 7.8-fold enhanced expression of TGF-beta
1 mRNA in liver cirrhosis in comparison with normal controls (p<0.01). By b
t situ hybridization, CTGF mRNA was detectable in only a few spindle cells
in the portal tracts in normal liver samples. In contrast, there was strong
expression of CTGF mRNA in fibroblasts and myofibroblast-like cells presen
t in fibrous septa surrounding the cirrhotic nodules, in stellate cells, in
endothelial cells and in mesenchymal cells around ductular proliferations,
and in ductular epithelial cells. There was a strong correlation between C
TGF mRNA and TGF-beta 1 mRNA as well as the degree of fibrosis (p<0.01). Co
nclusions: Overexpression of CTGF in liver cirrhosis, especially in fibrobl
asts/myofibroblasts and stellate cells, suggests that this novel factor may
play an important role in hepatic fibrosis.