亡识别受体调节小鼠皮肤组织的修复
Olivia Justynski1, Kate Bridges2, Will Krause1
1Dept. of Molecular Cellular and Developmental Biology, Yale University, New Haven, United States.
eLife
|December 21, 2023
概括
组织修复包括清除死细胞. 这项研究揭示了轴突信号传递对于小鼠的伤口愈合至关重要,与其在血细胞增生中的作用不同,为糖尿病伤口提供治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 再生医学是一种再生医学.
背景情况:
- 细胞亡和细胞灭对于组织修复至关重要,但它们的调节机制仍然不清楚.
- 了解这些过程对于解决糖尿病脚伤等疾病中愈合障碍至关重要.
研究的目的:
- 阐明亡细胞清除途径在早期伤口愈合中的作用.
- 确定改善慢性伤口修复的分子标,特别是糖尿病患者.
主要方法:
- 单细胞RNA测序小鼠皮肤伤口,绘制细胞动态图.
- 在小鼠体内对特定的乙细胞酶受体 (Axl,Timd4) 的抑制研究.
- 对人类糖尿病脚伤口基因表达的分析.
主要成果:
- 在小鼠伤口炎症期间,在纤维细胞和免疫细胞中发现的升高的亡途径和细胞受体 (包括Axl).
- 人类糖尿病伤口通过Axl/Gas6.6表现出改变的细胞体信号.
- 轴信号对于小鼠的伤口修复是必不可少的,独立于细胞分裂.
- 在小鼠中,Timd4的抑制会损害血细胞增生,并取消伤口修复.
结论:
- 亡细胞检测的独特机制协调组织修复.
- 轴突信号传递在伤口愈合中起着关键的非细胞作用.
- 针对 Axl 和 Timd4 路径可能为慢性和糖尿病性伤口提供治疗策略.
相关概念视频
The Extrinsic Apoptotic Pathway
6.4K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.4K
The Intrinsic Apoptotic Pathway
6.6K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K
Phagocytosis of Apoptotic Cells
3.8K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
3.8K
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
3.5K
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...
3.5K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K


