title: Blockade of CCN4 attenuates CCl4-induced liver fibrosis.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Xingfei
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, Yiwu Central Hospital, Zhejiang, China.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Lou
keywords: CCN4; carbon tetrachloride (CCl4); inflammation; liver fibrosis