title: Transforming Growth Factor-β Signaling Cascade Induced by Mechanical Stimulation of Fluid Shear Stress in Cultured Corneal Epithelial Cells.
abstract: Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs).
  
  
  
  The HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) with the parallel-plate type of flow chamber. Wound healing, cellular proliferation, growth factor expression, TGF-β1 concentration in the culture supernatant, and phosphorylation of SMAD2 were investigated.
  
  
  
  Monolayers of HCECs exposed to shear stress had delayed wound healing and decreased proliferation compared with those of the static control (0 dyne/cm2). With increasing shear stress, TGF-β1 expression and phosphorylation of SMAD2 increased significantly, but the levels of total TGF-β1 in the culture supernatant decreased significantly. Delayed wound healing, decreased proliferation, and phosphorylation of the SMAD2 by shear stress were canceled out with a TGF-β receptor inhibitor.
  
  
  
  Fluid shear stress on the HCECs affected TGF-β signaling, which was associated with delayed wound healing. Mechanical stress by blinking might involve TGF-β signaling, and activation of TGF-β might be a key factor in wound healing of the corneal epithelium. Further studies should investigate the molecular mechanism of shear stress-induced activation of TGF-β.
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Tsugiaki
authors.initials: T
authors.lastname: Utsunomiya
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishibazawa
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Nagaoka
authors.affiliation: Department of Medicine and Engineering Combined Research Institute, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Hanada
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Harumasa
authors.initials: H
authors.lastname: Yokota
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D065306:Corneal Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D010766:Phosphorylation; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D014945:Wound Healing / Q000502:physiology
chemical_list: C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D012313:RNA