title: Hydroxysafflor yellow A inhibits TGF-β1-induced activation of human fetal lung fibroblasts in vitro.
abstract: OBJECTIVE
  Hydroxysafflor yellow A (HSYA) is one of the chemical component isolated from Chinese medicine Carthamus tinctorius L. Our preliminary study confirmed that HSYA attenuated bleomycin-induced pulmonary fibrosis in mice. In this study, we evaluated the effect of HSYA on TGF-β1-induced activation of human fetal lung fibroblasts (MRC-5) and explored the underlying mechanisms of its activity.
  
  
  METHODS
  MRC-5 cells activated by TGF-β1 were incubated with HSYA and/or the TGF-β type I receptor inhibitor, SB431542. TGF-β1-induced cell proliferation, α-smooth muscle actin, collagen I alpha 1 and fibronectin expression, Smad, mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase/Akt signalling pathway activation were observed.
  
  
  RESULTS
  Hydroxysafflor yellow A significantly inhibited TGF-β1-induced cell proliferation and the expression, both mRNA and protein, of α-smooth muscle actin, collagen I alpha 1 and fibronectin. HSYA also suppressed TGF-β1 activation of Smad signal transduction via inhibition of Smad2 and Smad3 phosphorylation, their nuclear translocation and the binding activity of Smad3 to type I collagen promoter in MRC-5 cells. In addition, HSYA inhibited TGF-β1-induced phosphorylation of extracellular signal-regulated kinase (ERK). The inhibitory effects of HSYA were similar to SB431542.
  
  
  CONCLUSIONS
  These findings suggest that HSYA inhibits TGF-β1-induced activation of MRC-5 cells associated with TGF-β1/Smad and ERK/MAPK signalling pathways.
authors.affiliation: Department of Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang district, Beijing, 100029, China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang district, Beijing, 100029, China.
authors.forename: Yadan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang district, Beijing, 100029, China.
authors.forename: Baoxia
authors.initials: B
authors.lastname: Zang
authors.affiliation: Department of Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang district, Beijing, 100029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang district, Beijing, 100029, China. jm64456308@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Jin
mesh_terms: D000199:Actins / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C541116:ACTA2 protein, human; D000199:Actins; D001549:Benzamides; D024042:Collagen Type I; D004149:Dioxoles; D005353:Fibronectins; D011809:Quinones; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C085278:hydroxysafflor yellow A; D002599:Chalcone; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I
keywords: Smad; human fetal lung fibroblasts; hydroxysafflor yellow A; transforming growth factor-β1