Division of Cell and Developmental Biology, The University of Queensland, St. Lucia, QLD 4072, Australia; The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia.
Division of Cell and Developmental Biology, The University of Queensland, St. Lucia, QLD 4072, Australia.
Cell Rep. 2022 Feb 1;38(5):110316. doi: 10.1016/j.celrep.2022.110316.
Cell injury poses a substantial challenge for epithelia homeostasis. Several cellular processes preserve epithelial barriers in response to apoptosis, but less is known about other forms of cell death, such as pyroptosis. Here we use an inducible caspase-1 system to analyze how colon epithelial monolayers respond to pyroptosis. We confirm that sporadic pyroptotic cells are physically eliminated from confluent monolayers by apical extrusion. This is accompanied by a transient defect in barrier function at the site of the pyroptotic cells. By visualizing cell shape changes and traction patterns in combination with cytoskeletal inhibitors, we show that rapid lamellipodial responses in the neighbor cells are responsible for correcting the leakage and resealing the barrier. Cell contractility is not required for this resealing response, in contrast to the response to apoptosis. Therefore, pyroptosis elicits a distinct homeostatic response from the epithelium that is driven by the stimulation of lamellipodia in neighbor cells.
细胞损伤对上皮细胞稳态构成了重大挑战。有几种细胞过程可以保护上皮屏障免受细胞凋亡的影响，但对于其他形式的细胞死亡（如细胞焦亡）知之甚少。在这里，我们使用诱导型 caspase-1 系统来分析结肠上皮单层细胞如何对细胞焦亡做出反应。我们证实，散在的焦亡细胞通过顶端挤出从汇合的单层中被物理性清除。这伴随着焦亡细胞部位的屏障功能短暂缺陷。通过可视化细胞形状变化和牵引力模式并结合细胞骨架抑制剂，我们表明，相邻细胞中的快速片状伪足反应负责纠正渗漏并重新密封屏障。与细胞凋亡的反应不同，细胞收缩性不是这种再封闭反应所必需的。因此，细胞焦亡会引起上皮细胞的一种独特的稳态反应，这种反应是由相邻细胞中片状伪足的刺激所驱动的。
