The impact of CTGF on liver fibrosis

Backgrounds and aim
Liver fibrosis is a characteristic feature of liver cirrhosis. We previously reported that CTGF expression levels in cirrhotic livers were higher than those in chronic hepatitis livers. However, the impact of CTGF remains unclear. We aimed to clarify the significance of CTGF in fibrogenesis.
Materials and Methods
We generated hepatocyte-specific CTGF knockout mice (CTGFΔHep) and polyI:C-inducible CTGF knockout mice (CTGFΔLiver) by crossing Alb-Cre or Mx1-Cre Tg mice and CTGF^fl/fl mice. Some mice were performed bile duct ligation (BDL), administrated CCl4 twice a week or thioacetamide three times a week or fed with atherogenic diet.
Results
All mice treated with BDL, CCl4, thioacetamide or atherogenic diet showed increase of CTGF expression levels in their livers with fibrotic change. To examine the impact of CTGF on fibrogenesis, CTGFΔHep and CTGFΔLiver were treated with BDL. There was no difference in increased ALP, T-Bil and ALT levels between knockout mice and control mice at 3 weeks after BDL. However, while CTGF levels in BDL-operated CTGFΔHep did not significantly decrease compared with those in BDL-operated control mice, those in BDL-operated CTGFΔLiver did. Fibrotic change was also attenuated in BDL-operated CTGFΔLiver, evidenced by clo1a1 and col1a2 expression levels and liver tissues stained with Sirius Red. Similar results were obtained in CCl4-treated CTGFΔLiver.
Conclusions
CTGF was produced mainly in hepatic non-parenchymal cells under various fibrotic stimuli and exacerbated fibrosis. CTGF may be an important therapeutic target for liver fibrosis.