title: Coordinated Regulation of Palladin and α-Smooth Muscle Actin by Transforming Growth Factor-β in Human Corneal Fibroblasts.
abstract: OBJECTIVE
  To investigate the role of palladin in the cornea, we examined expression of this actin assembly-related protein in normal, diseased, or injured corneal tissue as well as in cultured corneal fibroblasts.
  
  
  METHODS
  Expression of palladin and α-smooth muscle actin (α-SMA) in the rat cornea with an incision wound, in the normal and diseased human cornea, and in cultured human corneal fibroblasts was examined by immunofluorescence or immunoblot analysis.
  
  
  RESULTS
  The expression of both palladin and α-SMA was detected at the lesion site during wound healing in the rat cornea. Whereas neither palladin nor α-SMA was detected in the normal human cornea, the colocalization of both proteins was detected in diseased human corneas with underlying conditions characterized by the presence of fibrosis. The expression of both palladin and α-SMA in cultured human corneal fibroblasts was increased by transforming growth factor-β (TGF-β) in a manner sensitive to inhibition by blockers of Smad or mitogen-activated protein kinase (MAPK) signaling. Finally, RNA interference-mediated depletion of palladin attenuated the TGF-β-induced upregulation of α-SMA expression in human corneal fibroblasts as well as TGF-β-induced collagen gel contraction mediated by these cells.
  
  
  CONCLUSIONS
  Palladin is expressed in the rat and human cornea in association with scar formation. Expression of palladin in human corneal fibroblasts is increased by TGF-β in a manner dependent on Smad and MAPK signaling and is required for the TGF-β-induced upregulation of α-SMA.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Morishige
authors.forename: Shizuka
authors.initials: S
authors.lastname: Murata
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Haruya
authors.initials: H
authors.lastname: Azumi
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Shin-Gyou-Uchi
authors.forename: Ken-Taro
authors.initials: KT
authors.lastname: Oki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Morita
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003316:Corneal Diseases / Q000378:metabolism*; D065306:Corneal Injuries / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000502:physiology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D003598:Cytoskeletal Proteins; C412722:PALLD protein, human; D010750:Phosphoproteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta