Protective role of DDIT4-mediated autophagy in dermal papilla cells after oxidative stress injury

Yuanyuan GAO; Hengguang ZHAO; Guihong YANG; Xia LEI

doi:10.16016/j.2097-0927.202406063

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Protective role of DDIT4-mediated autophagy in dermal papilla cells after oxidative stress injury

Basic Medicine | 更新时间：2026-01-09

- Protective role of DDIT4-mediated autophagy in dermal papilla cells after oxidative stress injury
- Journal of Army Medical University Vol. 46, Issue 21, Pages: 2397-2406(2024)
- 作者机构：
  
  1.400042 重庆，陆军特色医学中心皮肤科
  2.400010 重庆，重庆医科大学附属第二医院皮肤科
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation of China(82173440)
- DOI：10.16016/j.2097-0927.202406063
  CLC： R322.995;R966;R977.6
- Received：19 June 2024，
  
  Revised：2024-08-03，
  
  Published：15 November 2024
- 稿件说明：
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Yuanyuan GAO, Hengguang ZHAO, Guihong YANG, et al. Protective role of DDIT4-mediated autophagy in dermal papilla cells after oxidative stress injury[J]. Journal of Army Medical University, 2024, 46(21): 2397-2406.
DOI：

Yuanyuan GAO, Hengguang ZHAO, Guihong YANG, et al. Protective role of DDIT4-mediated autophagy in dermal papilla cells after oxidative stress injury[J]. Journal of Army Medical University, 2024, 46(21): 2397-2406. DOI： 10.16016/j.2097-0927.202406063.

摘要

目的

探索DNA损伤诱导转录因子4(DNA damage induced transcription factor 4，DDIT4)在毛乳头细胞氧化应激损伤中的保护作用及其机制。

方法

使用长波紫外线(ultraviolet radiation A，UVA)和过氧化氢(H

)建立毛乳头细胞氧化应激模型；CCK-8检测不同处理条件下的细胞活力，利用2′

7′-二氯荧光素二乙酸酯(2′

7′-dichlorofluorescein diacetate

DCFH-DA)试剂检测细胞内活性氧(ROS)的变化；电镜观察自噬小体；Western blot观察DDIT4及自噬相关指标微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3

LC3)、泛素结合蛋白(ubiquitin-binding protein P62

P62)、雷帕霉素哺乳动物靶蛋白(mammalian target of rapamycin

mTOR)、p-mTOR的表达情况。

结果

UVA和H

导致毛乳头细胞内ROS升高，活力下降(

＜0.05)；氧化应激环境下毛乳头细胞内的DDIT4表达增加(

＜0.05)，而抗氧化剂N-乙酰基-L-半胱氨酸(N-acetyl-L-cysteine

NAC)可有效抑制此效应(

＜0.05)；UVA或H

处理后毛乳头细胞内自噬水平升高，表现为自噬体数量增多，LC3Ⅱ/Ⅰ比值增高(

＜0.05)，P62表达下降(

＜0.05)，3-甲基腺嘌呤(3-methyladenine

3-MA)阻断自噬可观察到细胞活力进一步降低(

＜0.05)，细胞内ROS增多(

＜0.05)，反之，雷帕霉素(rapamycin

RAPA)可增加自噬水平提升氧化条件下毛乳头细胞活力，减少细胞内ROS生成(

＜0.05)；下调DDIT4表达可使氧化应激环境下毛乳头细胞自噬减弱，LC3Ⅱ/Ⅰ减少(

＜0.05)，p-mTOR/mTOR、P62增加(

＜0.05)，细胞活力下降(

＜0.05)，细胞内ROS增多(

＜0.05)。

结论

DDIT4可能通过自噬缓解毛乳头细胞氧化应激损伤。

Abstract

Objective

To explore the protective role of DNA damage induced transcription factor 4 (DDIT4) in oxidative stress injury in dermal papilla cells and its underlying mechanisms.

Methods

Dermal papilla cells were exposed to UVA and H

to establish cellular model of oxidative stress. CCK-8 assay was used to detect cell viability under different treatment conditions

and the production of intracellular reactive oxygen species (ROS) was detected using 2′

7′-dichlorofluorescein diacetate (DCFH-DA). Autophagic vesicles were observed with electron microscopy. Western blotting was employed to measure the expression of DDIT4 and autophagy-related molecules

including microtubule-associated protein 1 light chain 3 (LC3)

ubiquitin-binding protein (P62)

mammalian target of rapamycin (mTOR)

and p-mTOR.

Results

UVA and H

resulted in more production of ROS (

0.05) and decreased viability of dermal papilla cells (

0.05). DDIT4 expression was increased in dermal papilla cells under oxidative stress (

0.05)

and the antioxidant N-acetyl-L-cysteine (NAC) could effectively inhibit this effect (

0.05). After treatment with UVA or H

cell autophagy was enhanced in dermal papilla cells

characterized by an increase in the number of autophagosomes and an increased LC3Ⅱ/Ⅰ ratio (

0.05)

a decrease in P62 expression (

0.05)

and 3-methyladenine (3-MA) blocking autophagy led to further reduced cell viability (

0.05) and increased intracellular ROS production (

0.05). Conversely

rapamycin (RAPA) increased autophagy level and improved the viability of dermal papilla cells under oxidative conditions (

0.05)

and reduced the generation of intracellular ROS (

0.05). Additionally

down-regulation of DDIT4 weakened autophagy in dermal papilla cells under oxidative stress

reduced LC3Ⅱ/Ⅰ (

0.05)

increased p-mTOR/mTOR and P62 (

0.05)

inhibited cell viability (

0.05)

and enhanced intracellular ROS production (

0.05).

Conclusion

DDIT4 may alleviate oxidative stress injury in dermal papilla cells through autophagy.

关键词

Keywords

references

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