Expression and function of fibroblast growth factor-inducible 14 in human corneal myofibroblasts

Nobuyuki Ebihara, Masafumi Nakayama, Tomoko Tokura, Hiroko Ushio, Akira Murakami

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The interaction of fibroblast growth factor-inducible 14 (Fn14) and, its ligand tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to be important in wound healing of tissues. However, to our knowledge, expression and function of Fn14 in corneal myofibroblasts, which have a crucial role in wound healing of corneal stroma, has not been investigated. In this study, we investigated the expression and function of Fn14 in corneal myofibroblasts. Expression of Fn14 protein was assessed by flow cytometry. Corneal myofibroblasts showed strong expression of Fn14 protein, while keratocytes did not. TGF-β1 promoted the differentiation of keratocytes into corneal myofibroblasts, and induced Fn14 expression. These data reveal that keratocytes phenotype determines the level of Fn14 expression. ELISA was used to detect chemokines and matrix metalloproteinases in the supernatant of corneal myofibroblasts cultured with or without stimulation by TWEAK and/or TGF-β1. TWEAK increased the production of IL-8, MCP-1, and RANTES by corneal myofibroblasts via Fn14. TGF-β1 augmented the TWEAK-induced production of these chemokines. TWEAK also increased the production of MMP-1 and -3 by corneal myofibroblasts via Fn14, while TGF-β1 inhibited this effect of TWEAK on MMP production. TWEAK-induced phosphorylation of NF-κB and MAP kinase in corneal myofibroblasts. Furthermore, TWEAK partially inhibited the differentiation of keratocytes into corneal myofibroblasts promoted by TGF-β1. These data suggest that the Fn14/TWEAK system may have several roles in wound healing by corneal myofibroblasts. In the future, modulation of the TWEAK/Fn14 system may become a novel approach for control corneal wound healing.

Original languageEnglish
Pages (from-to)256-262
Number of pages7
JournalExperimental Eye Research
Volume89
Issue number2
DOIs
Publication statusPublished - 2009 Aug 1

Keywords

  • TGF-β
  • chemokines
  • corneal myofibroblast
  • fibroblast growth factor-inducible 14 (Fn14)
  • keratocytes
  • matrix metalloproteinases
  • tumor necrosis factor-like weak inducer of apoptosis (TWEAK)
  • wound healing

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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