Thrombomodulin promotes corneal epithelial wound healing

PLoS One. 2015 Mar 27;10(3):e0122491. doi: 10.1371/journal.pone.0122491. eCollection 2015.

Abstract

Purpose: To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing.

Methods: TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays.

Results: TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing.

Conclusions: TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Corneal Injuries / genetics*
  • Corneal Injuries / pathology
  • Corneal Injuries / therapy
  • Epithelium, Corneal / metabolism
  • Epithelium, Corneal / pathology
  • Mice
  • Proto-Oncogene Proteins c-sis / genetics*
  • Proto-Oncogene Proteins c-sis / metabolism
  • Recombinant Proteins / administration & dosage
  • Signal Transduction / drug effects
  • Thrombomodulin / administration & dosage
  • Thrombomodulin / biosynthesis
  • Thrombomodulin / genetics*
  • Wound Healing / drug effects
  • Wound Healing / genetics*

Substances

  • Proto-Oncogene Proteins c-sis
  • Recombinant Proteins
  • Thrombomodulin
  • Becaplermin

Grants and funding

This work was supported by the National Cheng Kung University Hospital Research Fund (NCKUH-10406017). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.