Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells

Fei Xiang; Pei Wang; Hao Gong; Jia Luo; Xin Zhou; Chenglin Zhan; Tianxing Hu; Mengru Wang; Yizhan Xing; Haiying Guo; Gaoxing Luo; Yuhong Li

doi:10.1093/burnst/tkac053

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Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells

更新时间：2023-08-29

- Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
  
  1. Institute of Burn Research
  2. Army Medical University
  3. Department of Cell Biology, Army Medical University
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkac053
  CLC：
- Published：2023，
  
  Published Online：3 July 2023，
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Fei Xiang, Pei Wang, Hao Gong, Jia Luo, Xin Zhou, Chenglin Zhan, Tianxing Hu, Mengru Wang, Yizhan Xing, Haiying Guo, Gaoxing Luo, Yuhong Li, Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells, Burns & Trauma, Volume 11, 2023, tkac053, https://doi.org/10.1093/burnst/tkac053
DOI：

Fei Xiang, Pei Wang, Hao Gong, Jia Luo, Xin Zhou, Chenglin Zhan, Tianxing Hu, Mengru Wang, Yizhan Xing, Haiying Guo, Gaoxing Luo, Yuhong Li, Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells, Burns & Trauma, Volume 11, 2023, tkac053, https://doi.org/10.1093/burnst/tkac053 DOI：

摘要

Abstract

BackgroundBurn wound healing is a complex process and the role of Wnt ligands varies in this process. Whether and how Wnt4 functions in burn wound healing is not well understood. In this study

we aim to reveal the effects and potential mechanisms of Wnt4 in burn wound healing.MethodsFirst

the expression of Wnt4 during burn wound healing was determined by immunofluorescence

Western blotting and qPCR. Then

Wnt4 was overexpressed in burn wounds. The healing rate and healing quality were analysed by gross photography and haematoxyline and eosin staining. Collagen secretion was observed by Masson staining. Vessel formation and fibroblast distribution were observed by immunostaining. Next

Wnt4 was knocked down in HaCaT cells. The migration of HaCaT cells was analysed by scratch healing and transwell assays. Next

the expression of β-catenin was detected by Western blotting and immunofluorescence. The binding of Frizzled2 and Wnt4 was detected by coimmunoprecipitation and immunofluorescence. Finally

the molecular changes induced by Wnt4 were analysed by RNA sequencing

immunofluorescence

Western blotting and qPCR in HaCaT cells and burn wound healing tissues.ResultsThe expression of Wnt4 was enhanced in burn wound skin. Overexpression of Wnt4 in burn wound skin increased the thickness of epidermis. Collagen secretion

vessel formation and fibroblast distribution were not significantly impacted by Wnt4 overexpression. When Wnt4 was knocked down in HaCaT cells

the ratio of proliferating cells decreased

the ratio of apoptotic cells increased and the ratio of the healing area in the scratch healing assay to the number of migrated cells in the transwell assay decreased. The nuclear translocation of β-catenin decreased in shRNA of Wnt4 mediated by lentivirus-treated HaCaT cells and increased in Wnt4-overexpressing epidermal cells. RNA-sequencing analysis revealed that cell junction-related signalling pathways were significantly impacted by Wnt4 knockdown. The expression of the cell junction proteins was decreased by the overexpression of Wnt4.ConclusionsWnt4 promoted the migration of epidermal cells. Overexpression of Wnt4 increased the thickness of the burn wound. A potential mechanism for this effect is that Wnt4 binds with Frizzled2 and increases the nuclear translocation of β-catenin

thus activating the canonical Wnt signalling pathway and decreasing the cell junction between epidermal cells.

关键词

Keywords

Wnt4Wnt signalling pathwayBurn wound healingCell junctionCell migration

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