Abstract
Corneal transparency, dependent on the integrity of epithelial cells, is essential for vision. Corneal epithelial damage is one of the most commonly observed ocular conditions and proper wound healing is necessary for corneal transparency. Sirt6, a histone deacetylase, has been shown to regulate many cellular events including aging and inflammation. However, its specific role in corneal epithelial wound healing remains unknown. Here we demonstrated that Sirt6 was expressed in corneal epithelial cells and its expression decreased with age. In an in vivo corneal epithelial wound healing model, Sirt6 deficiency resulted in delayed and incomplete wound healing and was associated excessive inflammation in the corneal stroma and dysfunction of Notch signaling, leading to keratinization of the corneal epithelium and corneal opacity. Aging Sirt6-deficient mice spontaneously developed corneal keratitis with extensive infiltration of inflammatory cells into the cornea. In vitro experiments demonstrated that primary corneal epithelial cells with Sirt6 downregulation expressed increased basal levels of inflammatory genes and exhibited hyper-inflammatory reactivity to IL-1β and TNFα treatment. These results provide compelling evidence that Sirt6 is a critical regulator of inflammation in the cornea, and is responsible for corneal epithelial wound healing, thus contributing to the maintenance of epithelial integrity and corneal transparency.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1932-1946 |
| Number of pages | 15 |
| Journal | Aging |
| Volume | 10 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2018 |
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Keywords
- Aging
- Cornea
- Epithelial wound healing
- Inflammation
- Sirt6
ASJC Scopus subject areas
- Aging
- Cell Biology
Cite this
Sirt6 deficiency impairs corneal epithelial wound healing. / Hu, Xiaobing; Zhu, Shuang; Liu, Rong; Miller, Jordan D; Merkley, Kevin; Tilton, Ronald G.; Liu, Hua.
In: Aging, Vol. 10, No. 8, 01.08.2018, p. 1932-1946.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sirt6 deficiency impairs corneal epithelial wound healing
AU - Hu, Xiaobing
AU - Zhu, Shuang
AU - Liu, Rong
AU - Miller, Jordan D
AU - Merkley, Kevin
AU - Tilton, Ronald G.
AU - Liu, Hua
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Corneal transparency, dependent on the integrity of epithelial cells, is essential for vision. Corneal epithelial damage is one of the most commonly observed ocular conditions and proper wound healing is necessary for corneal transparency. Sirt6, a histone deacetylase, has been shown to regulate many cellular events including aging and inflammation. However, its specific role in corneal epithelial wound healing remains unknown. Here we demonstrated that Sirt6 was expressed in corneal epithelial cells and its expression decreased with age. In an in vivo corneal epithelial wound healing model, Sirt6 deficiency resulted in delayed and incomplete wound healing and was associated excessive inflammation in the corneal stroma and dysfunction of Notch signaling, leading to keratinization of the corneal epithelium and corneal opacity. Aging Sirt6-deficient mice spontaneously developed corneal keratitis with extensive infiltration of inflammatory cells into the cornea. In vitro experiments demonstrated that primary corneal epithelial cells with Sirt6 downregulation expressed increased basal levels of inflammatory genes and exhibited hyper-inflammatory reactivity to IL-1β and TNFα treatment. These results provide compelling evidence that Sirt6 is a critical regulator of inflammation in the cornea, and is responsible for corneal epithelial wound healing, thus contributing to the maintenance of epithelial integrity and corneal transparency.
AB - Corneal transparency, dependent on the integrity of epithelial cells, is essential for vision. Corneal epithelial damage is one of the most commonly observed ocular conditions and proper wound healing is necessary for corneal transparency. Sirt6, a histone deacetylase, has been shown to regulate many cellular events including aging and inflammation. However, its specific role in corneal epithelial wound healing remains unknown. Here we demonstrated that Sirt6 was expressed in corneal epithelial cells and its expression decreased with age. In an in vivo corneal epithelial wound healing model, Sirt6 deficiency resulted in delayed and incomplete wound healing and was associated excessive inflammation in the corneal stroma and dysfunction of Notch signaling, leading to keratinization of the corneal epithelium and corneal opacity. Aging Sirt6-deficient mice spontaneously developed corneal keratitis with extensive infiltration of inflammatory cells into the cornea. In vitro experiments demonstrated that primary corneal epithelial cells with Sirt6 downregulation expressed increased basal levels of inflammatory genes and exhibited hyper-inflammatory reactivity to IL-1β and TNFα treatment. These results provide compelling evidence that Sirt6 is a critical regulator of inflammation in the cornea, and is responsible for corneal epithelial wound healing, thus contributing to the maintenance of epithelial integrity and corneal transparency.
KW - Aging
KW - Cornea
KW - Epithelial wound healing
KW - Inflammation
KW - Sirt6
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UR - http://www.scopus.com/inward/citedby.url?scp=85052596877&partnerID=8YFLogxK
U2 - 10.18632/aging.101513
DO - 10.18632/aging.101513
M3 - Article
C2 - 30070973
AN - SCOPUS:85052596877
VL - 10
SP - 1932
EP - 1946
JO - Aging
JF - Aging
SN - 1945-4589
IS - 8
ER -