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Sestrin2 inhibits YAP activation and negatively regulates corneal epithelial cell proliferation

Ji-Su Lee1,2, Hwan-Woo Park3, Kyong Jin Cho4

  • 1Myung-Gok Eye Research Institute, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, South Korea.

Experimental & Molecular Medicine
|June 13, 2020
PubMed

Insights

Sestrin2 negatively regulates corneal epithelial cell proliferation by suppressing YAP activity. Reduced Sestrin2 levels enhance wound healing in mice, offering potential therapeutic targets for corneal damage.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Corneal wound healing is critical for maintaining vision and relies on epithelial cell proliferation.
  • The molecular regulators of corneal epithelial cell proliferation remain incompletely understood.
  • Identifying these regulators is key to developing treatments for corneal damage.

Purpose of the Study:

  • To investigate the role of Sestrin2 in corneal epithelial wound healing.
  • To elucidate the molecular mechanisms by which Sestrin2 influences corneal epithelial cell proliferation.
  • To determine the relationship between Sestrin2, YAP, and reactive oxygen species in corneal repair.

Main Methods:

  • Analysis of Sestrin2 expression in corneal epithelium during wound healing.
  • Assessment of corneal epithelial cell proliferation in Sestrin2-deficient mice.
  • Investigation of YAP activation and localization in Sestrin2-deficient corneas.
  • Measurement of reactive oxygen species levels in the corneal epithelium.

Main Results:

  • Sestrin2 expression is downregulated during corneal wound healing.
  • Sestrin2-deficient mice exhibit enhanced corneal epithelial cell proliferation.
  • Sestrin2 acts as a negative regulator of YAP, a key mediator of the Hippo signaling pathway.
  • Increased reactive oxygen species in Sestrin2-deficient corneas promote YAP activation, enhancing cell proliferation.

Conclusions:

  • Sestrin2 is a novel negative regulator of YAP-mediated corneal epithelial cell proliferation.
  • The Sestrin2-YAP axis plays a significant role in corneal wound repair.
  • Targeting Sestrin2 may offer a therapeutic strategy for promoting corneal healing and treating epithelial damage.

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