Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival
Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival
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DOI：
10.1016/j.devcel.2021.05.007
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发表时间：
2021-06-22
影响因子：
11.8
通讯作者：
Pertz, Olivier
中科院分区：
文献类型：
--
作者：
Gagliardi, Paolo Armando;Dobrzynski, Maciej;Pertz, Olivier
细胞死亡事件不断挑战上皮屏障功能，但对于消除衰老或严重受损的细胞至关重要。这些凋亡事件如何在时空上组织起来以维持上皮细胞的稳态仍不清楚。我们观察了细胞外信号调节激酶（ERK）和AKT丝氨酸/苏氨酸激酶（Akt）活性脉冲的波，这些脉冲起源于凋亡细胞并径向传播到周围健康的细胞。这需要表皮生长因子受体（EGFR）和基质金属蛋白酶（MMP）信号传导。在单细胞水平，ERK/Akt波作为空间存活信号，局部保护上皮损伤附近的细胞免于凋亡，持续3-4小时。在细胞群体水平，ERK/ Akt波维持上皮细胞对轻度或强烈环境损伤的稳态（EH）。这种空间信号传导系统的破坏导致模型上皮组织不能确保响应于环境损伤的屏障功能。
Cell death events continuously challenge epithelial barrier function yet are crucial to eliminate old or critically damaged cells. How such apoptotic events are spatio-temporally organized to maintain epithelial homeostasis remains unclear. We observe waves of extracellular-signal-regulated kinase (ERK) and AKT serine/threonine kinase (Akt) activity pulses that originate from apoptotic cells and propagate radially to healthy surrounding cells. This requires epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP) signaling. At the single-cell level, ERK/Akt waves act as spatial survival signals that locally protect cells in the vicinity of the epithelial injury from apoptosis for a period of 3-4 h. At the cell population level, ERK/ Akt waves maintain epithelial homeostasis (EH) in response to mild or intense environmental insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to environmental insults.