Coordinated regulation of palladin and α-smooth muscle actin by transforming growth factor-β in human corneal fibroblasts

Naoyuki Morishige, Shizuka Murata, Yoshikuni Nakamura, Haruya Azumi, Ryutaro Shin-Gyou-Uchi, Ken Taro Oki, Yukiko Morita, Koh Hei Sonoda

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE. 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.

Original languageEnglish
Pages (from-to)3360-3368
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number7
DOIs
Publication statusPublished - Jun 1 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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