在慢性皮肤炎症中,Nrf2对表皮的剂量依赖作用
Michael Koch1, Luca Ferrarese1, Maya Ben-Yehuda Greenwald1
1Institute of Molecular Health Sciences, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland.
Disease models & mechanisms
|January 2, 2025
概括
在阿托皮性皮肤炎 (AD) 皮肤模型中NRF2活性降低会使DNA损伤和细胞衰老恶化. 然而,长期的NRF2激活会导致严重的皮肤问题,强调需要精确的治疗时间.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 亚托邦性皮肤炎 (AD) 涉及皮肤屏障缺陷和免疫变化.
- 在AD表皮中观察到细胞保护性NRF2转录因子的活性降低.
- 纤维细胞生长因子受体缺乏在角质细胞 (K5-R1 / R2小鼠) 模型AD类似的症状.
研究的目的:
- 调查NRF2缺乏在AD病变发生过程中的功能作用.
- 为了探索NRF2调节对AD类皮肤状况的影响.
主要方法:
- 对K5-R1/R2小鼠表皮进行蛋白质组学分析,以评估Nrf2活性.
- 基因操纵 (删除和激活) Nrf2 在角质细胞.
- 在皮肤上限时的药理 Nrf2 激活.
主要成果:
- 减少Nrf2活性与K5-R1/R2小鼠的DNA损伤增加和细胞衰老相关.
- Nrf2删除加剧了DNA损伤和衰老.
- 短期的Nrf2激活显示出轻微的保护作用.
- 长期的Nrf2激活导致过,表皮变厚,亡增加,免疫细胞概况发生变化.
结论:
- Nrf2在表皮平衡中扮演着复杂的,取决于环境的角色.
- 优化NRF2激活的持续时间和强度对于治疗AD相关的表皮变化至关重要.
相关概念视频
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
Clinical Applications of Epidermal Stem Cells
2.7K
Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own...
2.7K
Renewal of Skin Epidermal Stem Cells
2.5K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.5K
Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K
Inflammatory Response
1.8K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
1.8K


