Expression and significance of Fra-1 in healing of nitrogen mustard-induced skin wound in mice

Feng YE; Yuanpeng ZHAO; Jin CHENG; Mingliang CHEN; Guorong DAN; Zhongmin ZOU

doi:10.16016/j.1000-5404.201804202

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Expression and significance of Fra-1 in healing of nitrogen mustard-induced skin wound in mice

Military Medicine (the Project of Chongqing Press Fund in 2017) | 更新时间：2026-01-09

- Expression and significance of Fra-1 in healing of nitrogen mustard-induced skin wound in mice
- Journal of Third Military Medical University Vol. 40, Issue 20, Pages: 1820-1825(2018)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)军事预防医学系毒理学研究所
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scientists of China(81502711)
- DOI：10.16016/j.1000-5404.201804202
  CLC： R394.2;R758.25;R994.1
- Received：28 April 2018，
  
  Revised：2018-06-28，
  
  Published：30 October 2018
- 稿件说明：
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Feng YE, Yuanpeng ZHAO, Jin CHENG, et al. Expression and significance of Fra-1 in healing of nitrogen mustard-induced skin wound in mice[J]. Journal of Third Military Medical University, 2018, 40(20): 1820-1825.
DOI：

Feng YE, Yuanpeng ZHAO, Jin CHENG, et al. Expression and significance of Fra-1 in healing of nitrogen mustard-induced skin wound in mice[J]. Journal of Third Military Medical University, 2018, 40(20): 1820-1825. DOI： 10.16016/j.1000-5404.201804202.

摘要

目的

研究Fra-1在氮芥暴露鼠皮肤损伤修复进程中的表达及意义。

方法

建立氮芥损伤无毛小鼠皮肤模型，分别在1、3、7 d和14 d搜集皮肤样本，HE染色观察皮肤损伤修复的过程。蛋白印迹检测皮肤损伤各时间点Fra-1的动态变化，免疫组化检测Fra-1在皮肤中的表达定位。同时，体外实验采用siRNA转染角质形成细胞沉默Fra-1后，检测其对细胞迁移及氮芥诱导的炎症因子释放的影响。

结果

HE染色结果显示，氮芥损伤1 d后创缘处表皮结构紊乱，至7 d逐渐分化增厚。损伤后14 d，创缘处表皮细胞增多，且向损伤中心移行参与修复。组织蛋白印迹和免疫组化结果显示，损伤后3 d和14 d，Fra-1含量在表皮基底层中增加，且14 d时呈紧密分布。体外实验结果显示，20 μmol/L氮芥染毒10 h能显著降低细胞活性至80%(

0.01)；该剂量下细胞炎性因子IL-6在24 h，IL-1β在10 h/24 h均有增加。Fra-1 siRNA能有效沉默胞内Fra-1水平，同时抑制氮芥引起的IL-6表达，但对IL-1β的表达无显著影响。此外，Fra-1 siRNA对10 ng/mL EGF引起的细胞Fra-1蛋白增加和迁移水平加快均有明显的抑制作用(

0.01)。

结论

Fra-1可通过调控角质形成细胞炎性因子合成和迁移，参与氮芥诱导的皮肤损伤修复过程。

Abstract

Objective

To investigate the expression and significance of Fra-1 in the healing process of nitrogen mustard (NM)-induced skin wound in mice.

Methods

a mouse model of NM-induced skin injury was established. At 1

7 and 14 d after NM exposure

skin wound tissues were sampled to evaluate wound healing using HE staining. Western blotting was used to detect the dynamic changes of Fra-1 expression in the skin wound tissues

and immunohistochemistry was employed to characterize the distribution of Fra-1 in the tissues. In a HaCaT keratinocyte cell line

we tested the effect of Fra-1 knockdown by siRNA transfection on cell migration and NM-induced release of inflammatory factors.

Results

HE staining showed that degeneration and necrosis of the skin occurred at the center of the wound 1 d after NM exposure; at 7 d after the exposure

obvious damage of the epidermis structure was observed at the wound margins with gradual differentiation and thickening of the epidermis. At 14 days after NM exposure

epidermal cells increased at the wound margin and migrated to the center of the lesion to participate in wound healing. Western blotting and immunohistochemistry revealed significantly increased Fra-1 expression in the basal layer of the epidermis at 3 and 14 d after NM exposure

and showed a dense distribution of Fra-1 expression at 14 d. In cultured HaCaT cells

exposure to 20 μmol/L NM for 10 h significantly reduced the cell viability to 80% (

0.01); at this same dose

NM significantly increased IL-6 expression at 24 h and IL-1β expression at 10 and 24 h. Transfection of the cells with Fra-1 siRNA significantly inhibited NM-induced increase of IL-6 expression but did not significantly affect IL-1β expression. Treatment with 10 ng/mL epidermal growth factor markedly i

ncreased Fra-1 expression in HaCaT cells and accelerated the cell migration

and such effects were obviously suppressed by transfection of the cells with Fra-1 siRNA (

0.01).

Conclusions

Fra-1 participates in the healing of NM-induced skin wound possibly by regulating keratinocyte migration and inflammatory responses.

关键词

Keywords

references

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