S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion

Yu Zhang; Yajuan Song; Jing Du; Wei Liu; Chen Dong; Zhaosong Huang; Zhe Zhang; Liu Yang; Tong Wang; Shaoheng Xiong; Liwei Dong; Yaotao Guo; Juanli Dang; Qiang He; Zhou Yu; Xianjie Ma

doi:10.1093/burnst/tkad030

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S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion

更新时间：2024-02-04

- S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
  
  1. Department of Plastic Surgery
  2. Fourth Military Medical University
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad030
  CLC：
- Published：2023，
  
  Published Online：31 October 2023，
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Yu Zhang, Yajuan Song, Jing Du, Wei Liu, Chen Dong, Zhaosong Huang, Zhe Zhang, Liu Yang, Tong Wang, Shaoheng Xiong, Liwei Dong, Yaotao Guo, Juanli Dang, Qiang He, Zhou Yu, Xianjie Ma, S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion, Burns & Trauma, Volume 11, 2023, tkad030, https://doi.org/10.1093/burnst/tkad030
DOI：

Yu Zhang, Yajuan Song, Jing Du, Wei Liu, Chen Dong, Zhaosong Huang, Zhe Zhang, Liu Yang, Tong Wang, Shaoheng Xiong, Liwei Dong, Yaotao Guo, Juanli Dang, Qiang He, Zhou Yu, Xianjie Ma, S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion, Burns & Trauma, Volume 11, 2023, tkad030, https://doi.org/10.1093/burnst/tkad030 DOI：

摘要

Abstract

BackgroundIn plastic surgery

tissue expansion is widely used for repairing skin defects. However

low expansion efficiency and skin rupture caused by thin

expanded skin remain significant challenges in promoting skin regeneration during expansion. S100 calcium-binding protein A9 (S100A9) is essential in promoting wound healing; however

its effects on skin regeneration during tissue expansion remain unclear. The aim of the present study was to explore the role of S100A9 in skin regeneration

particularly collagen production to investigate its importance in skin regeneration during tissue expansion.MethodsThe expression and distribution of S100A9 and its receptors—toll-like receptor 4 (TLR-4) and receptor for advanced glycation end products were studied in expanded skin. These characteristics were investigated in skin samples of rats and patients. Moreover

the expression of S100A9 was investigated in stretched keratinocytes in vitro. The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed. TAK-242 was used to inhibit the binding of S100A9 to TLR-4; the levels of collagen I (COL I)

transforming growth factor beta (TGF-β)

TLR-4 and phospho-extracellular signal-related kinase 1/2 (p-ERK1/2) in fibroblasts were determined. Furthermore

fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I

TGF-β

TLR-4 and p-ERK1/2 in fibroblasts were investigated. Additionally

the area of expanded skin

thickness of the dermis

and synthesis of COL I

TGF-β

TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.ResultsIncreased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix (ECM) in the expanded dermis. Furthermore

S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-β in fibroblasts via the TLR-4/ERK1/2 pathway. We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I

TGF-β

TLR-4 and p-ERK1/2 expression in skin fibroblasts. Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.ConclusionsThese findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression. Our study laid the foundation for clinically improving tissue expansion using S100A9.

关键词

Keywords

S100 calcium-binding protein A9Skin Soft tissue expansionMechanical stretchRegeneration

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