Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction

Jie Zhang; Peilang Yang; Dan Liu; Min Gao; Jizhuang Wang; Tianyi Yu; Xiong Zhang; Yan Liu

doi:10.1093/burnst/tkab031

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Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction

更新时间：2022-06-14

- Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction
- Burns & Trauma Vol. 9, Issue 1, (2021)
- 作者机构：
  
  Department of Burn
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkab031
  CLC：
- Published：2021，
  
  Published Online：8 October 2021，
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Jie Zhang, Peilang Yang, Dan Liu, Min Gao, Jizhuang Wang, Tianyi Yu, Xiong Zhang, Yan Liu, Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction, Burns & Trauma, Volume 9, 2021, tkab031, https://doi.org/10.1093/burnst/tkab031
DOI：

Jie Zhang, Peilang Yang, Dan Liu, Min Gao, Jizhuang Wang, Tianyi Yu, Xiong Zhang, Yan Liu, Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction, Burns & Trauma, Volume 9, 2021, tkab031, https://doi.org/10.1093/burnst/tkab031 DOI：

摘要

Abstract

BackgroundDiabetic foot ulcers characterized by delayed healing are one of the main complications of diabetes. Epidermal keratinocyte dysfunction has been found to play a pivotal role in the poor healing ability of diabetic wounds. In this study

we aimed to explore the relationship between c-Myc and its O-linked N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) modification and keratinocyte dysfunction in diabetic wounds.MethodsClinical wound samples were collected and a full-thickness skin defect wound model of diabetic rats was established. Re-epithelialization of wounds was observed by H&E staining and expressions of proliferating cell nuclear antigen

transglutaminase 1

loricrin

c-Myc and O-GlcNAc were measured by immunohistochemistry. The functional changes of proliferation

migration and differentiation of human immortalized epidermal cells (HaCaT) cells after overexpression or knockdown of c-Myc were observed. O-GlcNAcylation of c-Myc was confirmed using immunoprecipitation and proximity ligation assay. Stability of the c-Myc protein was measured using cycloheximide. Wound healing was observed after topical application of compounds that inhibited c-Myc or O-GlcNAc on diabetic wounds.ResultsKeratinocytes at the diabetic wound margin were characterized by active proliferation and division

slow migration and poor differentiation. Similar phenomena were observed in HaCaT cells cultured in 30 mM glucose and keratinocytes at the wound margin of the diabetic rats. The expression of c-Myc was increased in keratinocytes at the wound margin of diabetic rats

patients

and in HaCaT cells cultured with 30 mM glucose. Increased expression of c-Myc promoted the proliferation while inhibiting the migration and differentiation of the HaCaT cells

and inhibition of c-Myc promoted diabetic wound healing. Increased O-GlcNAcylation of c-Myc with 30 mM glucose stabilized the c-Myc proteins. Inhibition of O-GlcNAc ameliorated keratinocyte dysfunction and promoted diabetic wound healing.ConclusionsIncreased expression of c-Myc promoted abnormal proliferation and inhibited migration and differentiation of keratinocytes at the diabetic wound margin. Increased O-GlcNAcylation of c-Myc with 30 mM glucose stabilized the c-Myc proteins. Inhibition of c-Myc or O-GlcNAc alleviated delayed diabetic wound healing. These findings make c-Myc and O-GlcNAc potential therapeutic targets for diabetic wounds.

关键词

Keywords

c-MycO-GlcNAcdiabetesWound healingkeratinocyteglucose

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