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- Title
Sestrin2 inhibits YAP activation and negatively regulates corneal epithelial cell proliferation.
- Authors
Lee, Ji-Su; Park, Hwan-Woo; Cho, Kyong Jin; Lyu, Jungmook
- Abstract
Corneal wound healing is essential for the maintenance of corneal integrity and transparency and involves a series of physiological processes that depend on the proliferation of epithelial cells. However, the molecular mechanisms that control corneal epithelial cell proliferation are poorly understood. Here, we show that Sestrin2, a stress-inducible protein, is downregulated in the corneal epithelium during wound healing and that the proliferation of epithelial basal cells is enhanced in Sestrin2-deficient mice. We also show that YAP, a major downstream effector of the Hippo signaling pathway, regulates cell proliferation during corneal epithelial wound repair and that Sestrin2 suppresses its activity. Moreover, increased levels of reactive oxygen species in the Sestrin2-deficient corneal epithelium promote the nuclear localization and dephosphorylation of YAP, activating it to enhance the proliferation of corneal epithelial cells. These results reveal that Sestrin2 is a negative regulator of YAP, which regulates the proliferative capacity of basal epithelial cells, and may serve as a potential therapeutic target for corneal epithelial damage. Eye injury: Healing corneal wounds Targeting a protein that suppresses cell proliferation may speed up the healing of wounds to the eye. The cornea forms a transparent coating over the iris and pupil, protecting the eye from injury. The molecular mechanisms that modulate the wound healing response in the outer layers of the cornea are unclear. Using human cells and mouse models, Jungmook Lyu at Konyang University, Daejeon, South Korea, and co-workers have uncovered the role of two proteins, Sestrin2 and YAP, in corneal repair. YAP regulates the cell proliferation needed for repair, but high levels of Sestrin2 can suppress YAP activity. The expression of Sestrin2 is naturally reduced during wound healing, and this activates both YAP and its associated pathways, speeding up the repair process. The researchers suggest Sestrin2 could be a useful therapeutic target.
- Publication
Experimental & Molecular Medicine EMM, 2020, Vol 52, Issue 6, p951
- ISSN
1226-3613
- Publication type
Article
- DOI
10.1038/s12276-020-0446-5