title: Vitamin D regulating TGF-β induced epithelial-mesenchymal transition.
abstract: BACKGROUND
  Subepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma. A critical regulator of fibrosis, transforming growth factor β (TGF-β), can induce airway remodeling in epithelial cells through induction of epithelial-mesenchymal transition (EMT). Vitamin D has immunomodulatory functions, however, its effect on controlling subepithelial fibrosis is not known.
  
  
  METHODS
  Human bronchial epithelial cells (BEAS-2B) were exposed to calcitriol followed by stimulation with TGF-β1 or TGF-β2. The protein expression and mRNA transcripts for E-cadherin, Snail, vimentin, and N-cadherin were analyzed by Western blot and qPCR. An invasion assay and scratch wound assay were performed to identify the migratory properties of the cells following treatments.
  
  
  RESULTS
  TGF-β1 decreased E-cadherin expression and increased protein expression and mRNA transcripts of Snail, vimentin, and N-cadherin together with increased cell invasion and migration. TGF-β2 elicited migratory response similar to TGF-β1 but induced the expression of EMT markers differently from that by TGF-β1. Calcitriol attenuated TGF-β1- and TGF-β2-induced cell motility. Also, calcitriol inhibited the expression of EMT markers in TGF-β1-treated epithelial cells with less effect on TGF-β2.
  
  
  CONCLUSIONS
  These data suggest that calcitriol inhibits both migration and invasion induced by TGF-β1 and TGF-β2 in human airway epithelial cells. However, the regulatory effect of vitamin D in epithelial-mesenchymal transition was more effective to TGF-β1-induced changes. Thus, calcitriol could be a potential therapeutic agent in the prevention and management of subepithelial fibrosis and airway remodeling.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA. kimfischer@creighton.edu.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Fischer
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA. DKAGR@creighton.edu.|Center for Clinical and Translational Science Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE, 68178, USA. DKAGR@creighton.edu.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D014746:Vimentin; D002117:Calcitriol