title: Berberine regulates proliferation, collagen synthesis and cytokine secretion of cardiac fibroblasts via AMPK-mTOR-p70S6K signaling pathway.
abstract: OBJECTIVE
  The traditional Chinese medicinal berberine has long been used to treat cardiovascular diseases; however, the mechanism underlying its effects remains unclear. Here, this study would to investigate the effects of berberine on proliferation, collagen synthesis and cytokine secretion of cardiac fibroblasts.
  
  
  METHODS
  We assessed proliferation, collagen synthesis and cytokine secretion in cardiac fibroblasts subjected to angiotensin II (Ang II) subsequent to the consumption of berberine or a control treatment. And then we detected the role of AMPK/mTOR signaling pathway in berberine treatment of cardiac fibroblasts.
  
  
  RESULTS
  In the present study, the cellular behaviors of cardiac fibroblasts induced by Ang II were significantly activated including proliferation, transformation into myofibroblasts and collagen synthesis. Additionally, the ability of cytokine secretion was enhanced obviously. It was demonstrated that treatment of cardiac fibroblasts with berberine resulted in deceased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen synthesis. And the protein secretion of TGFβ1 was inhibited; however, the protein secretion of IL-10 was increased in cardiac fibroblasts with berberine treatment. Mechanistically, the phosphorylation level of AMPK was increased; and the phosphorylation levels of mTOR and p70S6K were decreased in berberine treatment group.
  
  
  CONCLUSIONS
  These results illustrated that the protective effects of berberine on cellular behaviors of cardiac fibroblasts were at least in part due to activate AMPK signaling pathway and downregulate mTOR/p70S6K signaling pathway. Berberine might become a new strategy for treating cardiac fibrosis in the future.
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Ai
authors.affiliation: Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Guizhong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gui
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430014, Hubei Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016207:Cytokines; D001599:Berberine; D003094:Collagen
keywords: Berberine; cardiac fibroblasts; collagen synthesis; cytokine secretion; proliferation