Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.
Department of Chemistry, East Carolina University, 300 Science and Technology Building, Greenville, NC 27858-4353, USA.
Dev Cell. 2021 Jun 21;56(12):1712-1726.e6. doi: 10.1016/j.devcel.2021.05.007. Epub 2021 Jun 2.
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.
细胞死亡事件不断挑战上皮屏障功能，但对于清除衰老或严重受损的细胞至关重要。凋亡事件如何在时空上进行组织以维持上皮细胞稳态尚不清楚。我们观察到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，这些波起源于凋亡细胞，并向健康的周围细胞呈放射状传播。这需要表皮生长因子受体 (EGFR) 和基质金属蛋白酶 (MMP) 信号。在单细胞水平上，ERK/Akt 波作为空间存活信号，在 3-4 小时内局部保护上皮损伤附近的细胞免于凋亡。在细胞群体水平上，ERK/Akt 波维持上皮细胞稳态 (EH) 以应对轻度或强烈的环境刺激。破坏这种空间信号系统会导致上皮组织模型无法在环境刺激下确保屏障功能。
