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Sirt1 Regulates Corneal Epithelial Migration by Deacetylating Cortactin
Yong Lin1,2, Qi Liu1,2, Li Li1,2
1School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Investigative Ophthalmology & Visual Science
|November 9, 2022
Summary
Silent information regulator 1 (SIRT1) enhances corneal epithelial wound healing by promoting cell migration. Upregulation of SIRT1 deacetylates cortactin, boosting lamellipodia formation and accelerating healing.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Silent information regulator 1 (SIRT1) is an NAD+-dependent deacetylase involved in critical cellular processes.
- SIRT1 regulates metabolism, autophagy, and chromatin accessibility.
- Its role in corneal epithelial wound healing (CEWH) remains largely unexplored.
Purpose of the Study:
- To investigate the role of SIRT1 in corneal epithelial wound healing (CEWH).
- To elucidate the molecular mechanisms by which SIRT1 influences CEWH.
Main Methods:
- Generated corneal epithelial (CE)-specific Sirt1 deletion mice.
- Utilized a CE debridement model for CEWH.
- Employed Western blot, RT-qPCR, siRNA, scratch wound, MTS, TUNEL, co-immunoprecipitation, and immunofluorescence assays.
Main Results:
- SIRT1 expression increased during CEWH, correlating with decreased non-histone protein acetylation.
- SIRT1 deficiency impaired cell migration and delayed CEWH.
- SIRT1 directly deacetylated cortactin, and both proteins were crucial for lamellipodia formation and migration.
Conclusions:
- SIRT1 upregulation during CEWH deacetylates cortactin, enhancing corneal epithelial cell migration via lamellipodia formation.
- SIRT1 represents a potential therapeutic target for accelerating corneal epithelial wound healing.
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