title: Inhibition of osteopontin reduce the cardiac myofibrosis in dilated cardiomyopathy via focal adhesion kinase mediated signaling pathway.
abstract: BACKGROUND
  Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to a close relationship with cardiac fibrosis. Overexpression of OPN in cardiomyocytes induces dilated cardiomyopathy (DCM). This research is to study whether inhibition of OPN could reduce myocardial remodelling in DCM, and if this process is focal adhesion kinase (FAK) dependent, which is recently found an important signal molecule in fibrosis.
  
  
  METHODS
  Eight-week-old cTnTR141Wtransgenic mouse of DCM were injected with OPN-shRNA in left ventricular free wall, which could inhibit the OPN expression. Six weeks later, echocardiographic examinations were performed to test left ventricle function and heart tissues were harvested to test the quality of FAK by western blot and severity of fibrosis by masson staining. Human cardiac fibroblast was administrated with OPN, and FAK inhibition by PP2 was treated 2 h before OPN was given. Expression of α-SMA and collagen-I were tested by western blot and real-time PCR assay.
  
  
  RESULTS
  OPN-shRNA group has a relatively high ejection fraction (EF), fractional shortening (FS), LV free wall thickness and a less sever cardiac fibrosis. In vitro, OPN could increase collagen-I and α-SMA expression, and this process can be inhibited by FAK inhibitor.
  
  
  CONCLUSIONS
  Inhibition of OPN could reduce the LV remodeling and dysfunction in DCM mice, which may attribute to the suppression of collagen-I secretion in fibroblast through a FAK/Akt dependent pathway.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Tuo
authors.initials: T
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Guang-Pu
authors.initials: GP
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Pei-De
authors.initials: PD
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Cardiovascular Surgery Department, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 10037, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
keywords: Osteopontin (OPN); cardiac fibrosis; dilated cardiomyopathy (DCM); fibroblast; focal adhesion kinase (FAK)