title: Transforming growth factor beta 1 increases collagen content, and stimulates procollagen I and tissue inhibitor of metalloproteinase-1 production of dental pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling.
abstract: OBJECTIVE
  In order to clarify the role of transforming growth factor beta 1 (TGF-β1) in pulp repair/regeneration responses, we investigated the differential signaling pathways responsible for the effects of TGF-β1 on collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human dental pulp cells.
  
  
  METHODS
  Pulp cells were exposed to TGF-β1 with/without pretreatment and coincubation by 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)-benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling inhibitor). Sircol collagen assay was used to measure cellular collagen content. Culture medium procollagen I, TIMP-1, and MMP-3 levels were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  TGF-β1 increased the collagen content, procollagen I, and TIMP-1 production, but slightly decreased MMP-3 production of pulp cells. SB431542 and U0126 prevented the TGF-β1-induced increase of collagen content and TIMP-1 production of dental pulp cells.
  
  
  CONCLUSIONS
  These results indicate that TGF-β1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling.
authors.affiliation: Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Po-Shuen
authors.initials: PS
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Hsiao-Hua
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Chien-Yang
authors.initials: CY
authors.lastname: Yeh
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan City, Taiwan; Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan. Electronic address: mcchang@mail.cgust.edu.tw.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Chiu-Po
authors.initials: CP
authors.lastname: Chan
authors.affiliation: Department of Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Han-Yueh
authors.initials: HY
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Hsin-Cheng
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Wan-Chuen
authors.initials: WC
authors.lastname: Liao
authors.affiliation: School of Dentistry, University of Cardenal Herrera, CEU, Valencia, Spain.
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Jeng
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Sin-Yuet
authors.initials: SY
authors.lastname: Yeung
authors.affiliation: Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. Electronic address: jhjeng@ntu.edu.tw.
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology; D004149:Dioxoles / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000502:physiology; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D051785:Smad Proteins / Q000187:drug effects / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D002070:Butadienes; D024042:Collagen Type I; D004149:Dioxoles; D009570:Nitriles; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C113580:U 0126; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human
keywords: activin receptor-like kinase-5; collagen; dental pulp cells; signal transduction; tissue inhibitor of metalloproteinase-1; transforming growth factor beta