title: Annexin A2 promotes liver fibrosis by mediating von Willebrand factor secretion.
abstract: BACKGROUND
  Liver fibrosis can lead to cirrhosis and hepatocellular carcinoma if not treated in the early stages. The molecular mechanisms of the pathogenesis of hepatic fibrosis remain unclear.
  
  
  OBJECTIVE
  To identify the molecules involved in the pathogenesis of liver fibrosis and to investigate the potential effect and mechanism of Annexin A2 up-regulation during liver fibrosis progression.
  
  
  METHODS
  Twenty Sprague-Dawley rats were divided into two groups: the carbon tetrachloride (CCl4)-induced liver fibrosis group and the normal control group. Hematoxylin and eosin staining or Masson Trichrome staining and enzyme-linked immunosorbent assay were applied to assess the degree of liver damage and fibrosis in rats with CCl4-induced liver fibrosis. Liver tissue protein profiles were analyzed using iTRAQ and mass spectrometry. RT-PCR and western blotting analyses were employed to validate differentially expressed proteins. Small interfering RNA-based silencing was performed to study the function of Annexin A2.
  
  
  RESULTS
  Twelve weeks after CCl4injection, significant body weight changes and liver injury and liver fibrosis were observed in rats. In addition, 130 proteins were differentially expressed in the liver fibrosis group. Overexpression of Annexin A2 was confirmed by RT-PCR and Western blotting analysis. Silencing of Annexin A2 expression in HepG2 and LX-2 cells significantly reduced the secretion of von Willebrand factor (vWF).
  
  
  CONCLUSIONS
  Annexin A2 promotes liver fibrosis by mediating vWF secretion, which can be used to mitigate the progression of liver fibrosis.
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Reproductive Medical Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Sanglin
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xv
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Sha
authors.initials: S
authors.lastname: She
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ran
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Intensive Care Unit, The Second Hospital of Nanjing, Medicine School of Nanjing University, Jiangsu, China. Electronic address: doctor0219@163.com.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: yixuan.yang@hotmail.com.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020868:Gene Silencing; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism*; D013058:Mass Spectrometry; D011485:Protein Binding; D034741:RNA, Small Interfering; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D017306:Annexin A2; D034741:RNA, Small Interfering; D014841:von Willebrand Factor
keywords: Annexin A2; Isotope tags for relative and absolute quantification; Proteomics; von Willebrand factor