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Blockade of CCN4 attenuates CCl4-induced liver fibrosis.

Li X, Chen Y, Ye W, Tao X, Zhu J, Wu S, Lou L - Arch Med Sci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Protein expression levels of pro-fibrotic factors (A) α-SMA and (B) TGF-β1. Chronic CCl4 treatment up-regulated the protein expression of α-SMA and TGF-β1 (*p < 0.001). The protein expression levels were expressed as the ratio of band intensity for target protein relative to that for internal control (β-tubulin), n = 12 mice per group.*P < 0.01, compared with vehicle-treated normal control; **p < 0.01 compared with CCl4-treated group
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Figure 0006: Protein expression levels of pro-fibrotic factors (A) α-SMA and (B) TGF-β1. Chronic CCl4 treatment up-regulated the protein expression of α-SMA and TGF-β1 (*p < 0.001). The protein expression levels were expressed as the ratio of band intensity for target protein relative to that for internal control (β-tubulin), n = 12 mice per group.*P < 0.01, compared with vehicle-treated normal control; **p < 0.01 compared with CCl4-treated group

Mentions: Chronic treatment with CCl4 enhanced the protein expression levels of α-SMA (0.17 ±0.08 vs. 0.68 ±0.12 vs. 0.21 ±0.09, p < 0.01, Figure 6 A) and TGF-β1 (0.09 ±0.05 vs. 0.45 ±0.11 vs. 0.18 ±0.09, p < 0.01, p < 0.01, Figure 6 B). CCN4mAb treatment significantly down-regulated the expression levels of these pro-fibrotic markers (p < 0.01).


Blockade of CCN4 attenuates CCl4-induced liver fibrosis.

Li X, Chen Y, Ye W, Tao X, Zhu J, Wu S, Lou L - Arch Med Sci (2015)

Protein expression levels of pro-fibrotic factors (A) α-SMA and (B) TGF-β1. Chronic CCl4 treatment up-regulated the protein expression of α-SMA and TGF-β1 (*p < 0.001). The protein expression levels were expressed as the ratio of band intensity for target protein relative to that for internal control (β-tubulin), n = 12 mice per group.*P < 0.01, compared with vehicle-treated normal control; **p < 0.01 compared with CCl4-treated group
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495160&req=5

Figure 0006: Protein expression levels of pro-fibrotic factors (A) α-SMA and (B) TGF-β1. Chronic CCl4 treatment up-regulated the protein expression of α-SMA and TGF-β1 (*p < 0.001). The protein expression levels were expressed as the ratio of band intensity for target protein relative to that for internal control (β-tubulin), n = 12 mice per group.*P < 0.01, compared with vehicle-treated normal control; **p < 0.01 compared with CCl4-treated group
Mentions: Chronic treatment with CCl4 enhanced the protein expression levels of α-SMA (0.17 ±0.08 vs. 0.68 ±0.12 vs. 0.21 ±0.09, p < 0.01, Figure 6 A) and TGF-β1 (0.09 ±0.05 vs. 0.45 ±0.11 vs. 0.18 ±0.09, p < 0.01, p < 0.01, Figure 6 B). CCN4mAb treatment significantly down-regulated the expression levels of these pro-fibrotic markers (p < 0.01).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus