Connective tissue growth factor in human liver cirrhosis

M Abou‐Shady, H Friess, A Zimmermann, FF Di Mola… - Liver, 2000 - Wiley Online Library
M Abou‐Shady, H Friess, A Zimmermann, FF Di Mola, XZ Guo, HU Baer, MW Büchler
Liver, 2000Wiley Online Library
Background: Connective tissue growth factor (CTGF) belongs to a family of factors that
regulate fibrogenesis and wound healing. While the significance of transforming growth
factor beta (TGF‐β) in liver fibrosis is well established, the role of CTGF in fibrosing
hepatopathy is still unknown. Methods: CTGF was analyzed in 10 normal and in 16 cirrhotic
liver tissue samples. Northern blot analysis was used to examine the concomitant
expression of CTGF and TGF‐β1 mRNAs, and the cellular localization of CTGF mRNA was …
Background
Connective tissue growth factor (CTGF) belongs to a family of factors that regulate fibrogenesis and wound healing. While the significance of transforming growth factor beta (TGF‐β) in liver fibrosis is well established, the role of CTGF in fibrosing hepatopathy is still unknown.
Methods
CTGF was analyzed in 10 normal and in 16 cirrhotic liver tissue samples. Northern blot analysis was used to examine the concomitant expression of CTGF and TGF‐β1 mRNAs, and the cellular localization of CTGF mRNA was studied by in situ hybridization. For identification of myofibroblasts and activated hepatic stellate cells, α‐smooth muscle actin (α‐SMA) immunohistochemistry was used.
Results
Northern blot analysis showed 6.5‐fold enhanced expression of CTGF mRNA and 7.8‐fold enhanced expression of TGF‐β1 mRNA in liver cirrhosis in comparison with normal controls (p<0.01). By in 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 present 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 CTGF mRNA and TGF‐β1 mRNA as well as the degree of fibrosis (p<0.01).
Conclusions
Overexpression of CTGF in liver cirrhosis, especially in fibroblasts/myofibroblasts and stellate cells, suggests that this novel factor may play an important role in hepatic fibrosis.
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