The role of the Nrf2-mediated defense system in corneal epithelial wound healing

Ryuhei Hayashi, Noriko Himori, Keiko Taguchi, Yuki Ishikawa, Kohji Uesugi, Miyuki Ito, Thomas Duncan, Motokazu Tsujikawa, Toru Nakazawa, Masayuki Yamamoto, Kohji Nishida

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


The corneal epithelium exists at the surface of cornea and is easily damaged by external stresses such as UV radiation or physical injury. The Nrf2-mediated defense system plays a central role in protecting cells by activating genes against these types of stress. In this study, we investigated the role of the Nrf2-mediated defense system in corneal epithelial wound healing by using Nrf2-knockout (KO) mice. Nrf2 was expressed in the corneal epithelium of wild-type (WT) mice, but not in KO mice. Observation of wounds after 24 h of healing revealed that healing of the corneal epithelium was significantly delayed in the Nrf2 KO mice, whereas Nrf2 was activated in the corneal epithelium of WT mice. Ki-67 staining revealed that the number of Ki-67-positive proliferating cells was significantly lower in the Nrf2 KO mice than in the WT mice at 24-36 h after injury; however, these numbers were approximately equivalent by 48 h. To clarify the role of Nrf2 during wound healing, we performed in vitro experiments with siRNA for Nrf2 and its suppressor Keap1. Nrf2 knockdown significantly delayed corneal epithelial cell migration, but did not affect cell proliferation. Conversely, Keap1 knockdown significantly accelerated cell migration. These results suggest that Nrf2 contributed to the corneal epithelial wound-healing process by accelerating cell migration, and Nrf2 would therefore be a good target for the treatment of corneal epithelial diseases such as dry eye or chronic corneal epithelial defect.

Original languageEnglish
Pages (from-to)333-342
Number of pages10
JournalFree Radical Biology and Medicine
Publication statusPublished - 2013


  • Cell migration
  • Cell proliferation
  • Corneal epithelium
  • Free radicals
  • Keap1
  • Nrf2
  • Wound healing


Dive into the research topics of 'The role of the Nrf2-mediated defense system in corneal epithelial wound healing'. Together they form a unique fingerprint.

Cite this