title: Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn.
abstract: Corneal wound healing involves a complex cascade of cytokine-controlled cellular events, including inflammatory and angiogenesis responses that are regulated by transcriptional chromatin remodeling. Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate (NUCKS) is a key chromatin modifier and transcriptional regulator of metabolic signaling. In this study, we investigated the role of NUCKS in corneal wound healing by comparing its effects on corneal alkali burn in NUCKS knockout (NKO) and NUCKS wild-type (NWT) mice. Our data showed that following alkali-injury, inhibition of NUCKS (NKO) accelerated ocular resurfacing and suppressed neovascularization; the cytokine profile of alkali burned corneas in NKO mice showed suppressed expression of inflammation cytokines (IL1A &IL1B); upregulated expression of antiangiogenic factor (Pigment Epithelium-derived Factor; PEDF); and downregulated expression of angiogenic factor (Vascular Endothelial Growth Factor, VEGF); in vitro, following LPS-induced NFκB activation, NKO corneal cells showed reduced expression of IL6, IP10 and TNFα. In vitro, corneal epithelial cells showed reduced NF-κb activation on silencing of NUCKS and corresponding NFκB-mediated cytokine expression was reduced. Here, we illustrate that inhibition of NUCKS played a role in cytokine modulation and facilitated corneal recovery. This reveals a potential new effective strategy for ocular burn treatment.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.|Shenzhen Institutes of Research and Innovation, the University of Hong Kong, Hong Kong SAR, China.|Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ming-Wai
authors.initials: MW
authors.lastname: Poon
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qin
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Molecular and Cellular Biology, Biopolis, Singapore.
authors.forename: Beiying
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Infectious &Inflammatory Disease Center, the Burnham Institute for Medical Research, La Jolla, California, U.S.
authors.forename: Sumit
authors.initials: S
authors.lastname: Chanda
authors.affiliation: Institute of Molecular and Cellular Biology, Biopolis, Singapore.
authors.forename: Vinay
authors.initials: V
authors.lastname: Tergaonkar
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ian Y
authors.initials: IY
authors.lastname: Wong
authors.affiliation: Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: David S H
authors.initials: DS
authors.lastname: Wong
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.|Shenzhen Institutes of Research and Innovation, the University of Hong Kong, Hong Kong SAR, China.|Department of Ophthalmology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
mesh_terms: D000818:Animals; D002057:Burns, Chemical; D002478:Cells, Cultured; D065306:Corneal Injuries / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism; D005126:Eye Burns / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D016328:NF-kappa B; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C000591522:Nucks1 protein, mouse; C467480:vascular endothelial growth factor A, mouse