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Blockade of CCN4 attenuates CCl4-induced liver fibrosis
Xiaofei Li1, Yongxin Chen1, Weiwei Ye1
1Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
Introduction:
CCN4, also termed WNT-inducible signaling pathway protein-1 (WISP-1), has important roles in inflammation and tissue injury. This study aimed to investigate the effect of CCN4 inhibition using monoclonal anti-CCN4 antibody (CCN4mAb) on the liver injury and fibrosis in a mouse model of liver fibrosis.
Material And Methods:
The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received vehicle (saline/olive oil) by subcutaneous injection, CCl4 by subcutaneous injection or CCl4 (subcutaneous) plus CCN4mAb by subcutaneous injection. The pro-inflammatory and pro-fibrotic factors were determined by Western blot. The biochemistry and histopathology, collagen deposition and nuclear factor (NF)-κB activity were also assessed.
Results:
Chronic CCl4 treatment caused liver injury and collagen accumulation. The expression levels of CCN4, pro-inflammatory and pro-fibrotic mediators as well as the activity of NF-κB were markedly increased. Treatment with CCN4mAb significantly inhibited CCl4-induced CCN4 expression, leading to attenuated CCl4-induced liver injury and the inflammatory response. CCN4 blockade also significantly reduced the formation of collagen in the liver and the expression of α-smooth muscle actin and transforming growth factor β1.
Conclusions:
CCN4 inhibition by CCN4mAb in vivo significantly attenuated the CCl4-induced liver injury and the progression of liver fibrosis. CCN4 may represent a novel therapeutic target for liver injury and fibrosis.
Insights
Inhibiting CCN4 with an antibody significantly reduced liver injury and fibrosis in mice. This suggests CCN4 is a potential therapeutic target for treating liver damage and scarring.
Area of Science:
- Hepatology
- Immunology
- Molecular Biology
Background:
- CCN4 (WISP-1) plays a role in inflammation and tissue injury.
- Liver fibrosis is a condition characterized by excessive collagen deposition.
- Understanding CCN4's role in liver fibrosis is crucial for developing new treatments.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting CCN4.
- To evaluate the effect of a monoclonal anti-CCN4 antibody (CCN4mAb) on liver injury and fibrosis.
Main Methods:
- A mouse model of liver fibrosis was induced using carbon tetrachloride (CCl4).
- Mice were treated with CCl4 alone or CCl4 plus CCN4mAb.
- Key inflammatory and fibrotic markers, including NF-κB activity and collagen deposition, were assessed.
Main Results:
- CCl4 induced significant liver injury, inflammation, and fibrosis, increasing CCN4 expression and NF-κB activity.
- CCN4mAb treatment markedly reduced CCl4-induced CCN4 expression, liver injury, and inflammation.
- CCN4 blockade also significantly decreased collagen formation, α-smooth muscle actin, and transforming growth factor β1.
Conclusions:
- CCN4 inhibition effectively attenuated CCl4-induced liver injury and fibrosis progression in vivo.
- CCN4 represents a promising therapeutic target for liver injury and fibrosis.
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