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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

Sirius Red staining on the sections of (A) vehicle-treated normal control, (B) CCl4-treated and (C) CCl4 + CCN4mAb-treated groups. Histograms show the percentage area of Sirius Red staining of collagen of (D) whole liver section, (E) along central vein and (F) pericellular area. CCl4 treatment increased collagen deposition in central vein and pericellular area&p < 0.01, versus vehicle-treated normal control; &&p < 0.01 compared with CCl4-treated group (n = 10–12/group).
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Figure 0003: Sirius Red staining on the sections of (A) vehicle-treated normal control, (B) CCl4-treated and (C) CCl4 + CCN4mAb-treated groups. Histograms show the percentage area of Sirius Red staining of collagen of (D) whole liver section, (E) along central vein and (F) pericellular area. CCl4 treatment increased collagen deposition in central vein and pericellular area&p < 0.01, versus vehicle-treated normal control; &&p < 0.01 compared with CCl4-treated group (n = 10–12/group).

Mentions: Chronic CCl4 treatment showed a significant increase in collagen accumulation in the liver (0.37 ±0.04 vs. 2.14 ±0.22 vs. 0.91 ±0.24, p < 0.01, Figure 3 D). The deposition of collagen in the pericellular area and along the central vein was profoundly elevated (p < 0.01) (respectively 0.26 ±0.07 vs. 1.08 ±0.18 vs. 0.54 ±0.14, p < 0.01, Figure 3 E and 0.13 ±0.02 vs. 1.26 ±0.15 vs. 0.42 ±0.19, p < 0.01, Figure 3 F). Overall, the total amount of collagen was markedly increased in group 2. Treatment with CCN4mAb resulted in an obvious reduction of collagen accumulation within the liver compared with group 2 (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)

Sirius Red staining on the sections of (A) vehicle-treated normal control, (B) CCl4-treated and (C) CCl4 + CCN4mAb-treated groups. Histograms show the percentage area of Sirius Red staining of collagen of (D) whole liver section, (E) along central vein and (F) pericellular area. CCl4 treatment increased collagen deposition in central vein and pericellular area&p < 0.01, versus vehicle-treated normal control; &&p < 0.01 compared with CCl4-treated group (n = 10–12/group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4495160&req=5

Figure 0003: Sirius Red staining on the sections of (A) vehicle-treated normal control, (B) CCl4-treated and (C) CCl4 + CCN4mAb-treated groups. Histograms show the percentage area of Sirius Red staining of collagen of (D) whole liver section, (E) along central vein and (F) pericellular area. CCl4 treatment increased collagen deposition in central vein and pericellular area&p < 0.01, versus vehicle-treated normal control; &&p < 0.01 compared with CCl4-treated group (n = 10–12/group).
Mentions: Chronic CCl4 treatment showed a significant increase in collagen accumulation in the liver (0.37 ±0.04 vs. 2.14 ±0.22 vs. 0.91 ±0.24, p < 0.01, Figure 3 D). The deposition of collagen in the pericellular area and along the central vein was profoundly elevated (p < 0.01) (respectively 0.26 ±0.07 vs. 1.08 ±0.18 vs. 0.54 ±0.14, p < 0.01, Figure 3 E and 0.13 ±0.02 vs. 1.26 ±0.15 vs. 0.42 ±0.19, p < 0.01, Figure 3 F). Overall, the total amount of collagen was markedly increased in group 2. Treatment with CCN4mAb resulted in an obvious reduction of collagen accumulation within the liver compared with group 2 (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