title: Osthole inhibits the expressions of collagen I and III through Smad signaling pathway after treatment with TGF-β1 in mouse cardiac fibroblasts.
abstract: BACKGROUND
  Osthole, a natural coumarin and bioactive compound isolated from the fruit of Cnidium monnieri (L.) Cusson, was reported to prevent isoprenaline-induced myocardial fibrosis in mice by inhibiting the transforming growth factor-β1 (TGF-β1) expression, but the underlying mechanism is still unclear. The aim of this study is to illuminate whether the mechanism of osthole inhibiting collagen I and III expressions is associated with Smad signaling pathway in mouse cardiac fibroblasts (CFs) treated with TGF-β1.
  
  
  METHODS
  The mouse CFs stimulated with TGF-β1 were cultured and treated with osthole 1.25-5μg/ml for 24h. The expressions of α-SMA, collagen I, collagen III, TGF-β receptor I (TβRI), Smad2/3, phospho-Smad2/3 (P-Smad2/3), Smad4 and Smad7 were detected by real-time PCR method and western blot method, respectively.
  
  
  RESULTS
  After treatment with TGF-β1 and osthole in CFs, the levels of α-SMA expression and collagen I and III were reduced by osthole treatment. Accordingly, the ratio of collagen I/III had a similar changing trend. Besides, the levels of TβRI, Smad2/3, P-Smad2/3 and Smad4 expressions were decreased, while the level of Smad7 expression was increased after treatment with osthole.
  
  
  CONCLUSIONS
  The present results demonstrated that osthole could inhibit the collagen I and III expressions and their ratio in CFs treated with TGF-β1 via Smad signaling pathway, which might be one of its anti-fibrotic action mechanisms.
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
authors.forename: Jin-Cheng
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Xie
authors.affiliation: Clinic Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Zong-Qi
authors.initials: ZQ
authors.lastname: Cheng
authors.affiliation: Clinic Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Clinic Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Clinic Pharmacology Laboratory, Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: rongchen_76@aliyun.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics*; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics*; D003374:Coumarins / Q000494:pharmacology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D003374:Coumarins; D012333:RNA, Messenger; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D053773:Transforming Growth Factor beta1; C046627:osthol
keywords: Collagen I; Collagen III; Osthole; Smad; TGF-β1