对Hippo-YAP通路激活的机制性见解,以增强DFU愈合的功能
Shaochun Zhang1, Ye Wang1, Xuesong Xiong2
1Department of Orthopedics, The Central Hospital of Ezhou, Ezhou 436000, China.
American journal of physiology. Cell physiology
|April 22, 2025
概括
TFAP2A-LIFR-Hippo-YAP通路促进M2巨细胞的两极分化,加速糖尿病足的愈合. 这一途径是慢性伤口治疗的有希望的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 伤口治愈研究研究 伤口治愈研究
背景情况:
- 糖尿病足 (DFU) 是一个日益严重的全球健康问题,影响患者的生活质量和医疗保健系统.
- M2极化巨细胞对于组织修复和解决伤口愈合过程中的炎症至关重要.
研究的目的:
- 研究TFAP2A-LIFR-Hippo-YAP信号轴在调节巨细胞M2极化中的作用及其在DFU伤口愈合中的功能.
- 为了确定慢性糖尿病伤口的新型治疗点.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和批量RNA测序用于分析DFU样本中的免疫细胞子集.
- 在体外实验中评估了TFAP2A对巨细胞极化和内皮细胞功能的影响.
- 用小鼠模型来评估TFAP2A-LIFR-Hippo-YAP轴对DFU伤口愈合的影响.
主要成果:
- 巨被通过scRNA-seq.识别为DFU样本中的关键调节细胞.
- 发现TFAP2A可以促进M2巨细胞的两极分化 (通过ARG1表达表示) 并改善内皮功能.
- 证明TFAP2A-LIFR-Hippo-YAP轴通过诱导M2极化来加速DFU伤口愈合.
结论:
- TFAP2A-LIFR-Hippo-YAP信号轴在糖尿病足治愈中发挥着关键的免疫调节作用.
- 在DFU中,TFAP2A是巨细胞M2极化和血管生成的关键调节者.
- 这一途径代表了增强慢性糖尿病伤口愈合的有希望的治疗标.
相关概念视频
Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Overview of Regeneration and Repair
Regeneration and repair processes are critical in healing damages caused by injury, disease, and aging. In regeneration, the damaged tissue is entirely replaced with new growth that restores the original architecture and function. In contrast, tissue repair usually results in a fixed tissue architecture involving scar formation. Scars generally do not reestablish tissue function and may also exhibit structural abnormalities at the injury site.
Regeneration
All animals have varying degrees of...
Regeneration
All animals have varying degrees of...


