From start to finish-a molecular link in wound repair.
From start to finish-a molecular link in wound repair.
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从开始到结束——伤口修复的分子环节。
DOI：
10.1126/science.abn7411
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Greco,Valentina
中科院分区：
文献类型：
--
作者：
Yun,Sangwon;Greco,Valentina
在上皮伤口修复过程中，当上皮片集体迁移以关闭间隙时，一部分上皮细胞成为“领导者”。这些领导细胞采用不同的形态特征和上调迁移途径（,），但这一亚群从同质群体中出现的分子机制仍有待阐明。在本刊628页，Kozyrskaet等人发现，领导细胞的行为始于肿瘤抑制因子和转录因子p53的激活，从而诱导p21的表达和伴随的细胞周期抑制。一旦损伤得到解决，领导细胞通过p53依赖性拥挤超敏反应被消除。通常情况下，p53会被细胞应激源激活，包括DNA损伤、致癌表达和缺氧。在损伤造成机械破坏的情况下，p53通过应激激酶p38激活。这些新发现的p53在领导细胞出现和消除中的作用为伤口修复提供了重要的见解。
During epithelial wound repair, a subset of epithelial cells become “leaders” as the epithelial sheet collectively migrates to close the gap. These leader cells adopt distinct morphological characteristics and up-regulate migratory pathways (, ), but the molecular mechanism by which this subset emerges from an otherwise homogeneous population remained to be elucidated. On page 628 of this issue, Kozyrskaet al.find that leader cell behavior initiates with the activation of the tumor suppressor and transcription factor p53, which induces p21 expression and attendant cell cycle inhibition. Once the injury is resolved, leader cells are eliminated through p53-dependent crowding hypersensitivity. Classically, p53 becomes activated by cell stressors, including DNA damage, oncogenic expression, and hypoxia . In the case of mechanical disruption from wounding, p53 activation occurs through the stress kinase p38 . These newly found roles of p53 in leader cell emergence and elimination provide important insight into wound repair.