Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells, which regulates macrophage phenotype after injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of Nras and Bcas2 , both of which positively promoted epithelial proliferation and tissue regeneration in vivo. We also established that this role of Panx1 in boosting epithelial repair after injury is conserved between mouse lung and zebrafish tailfin. These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration after injury.

中文翻译：

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Pannexin 1 在组织损伤后驱动有效的上皮修复

肺和皮肤等上皮组织暴露在环境中，因此在受伤或感染期间特别容易受到损害。因此，快速修复对于恢复功能和器官稳态至关重要。失调的上皮组织修复发生在几种人类疾病状态中，但尚未完全了解单个细胞类型如何交流和相互作用以协调组织再生。在这里，我们展示了 pannexin 1 (Panx1)，一种由垂死细胞中的半胱天冬酶激活的细胞膜通道，通过调节损伤诱导的上皮增殖来驱动组织损伤后有效的上皮再生。肺气道上皮损伤促进垂死上皮细胞依赖 Panx1 释放 ATP 等因子，从而调节损伤后的巨噬细胞表型。这个过程反过来，诱导组织巨噬细胞的修复反应，包括诱导可溶性丝裂原双调蛋白，促进损伤诱导的上皮细胞增殖。再生肺上皮的分析确定了 Panx1 依赖性诱导Nras和Bcas2，两者都在体内积极促进上皮增殖和组织再生。我们还确定 Panx1 在损伤后促进上皮修复中的这种作用在小鼠肺和斑马鱼尾鳍之间是保守的。这些数据确定了上皮细胞和巨噬细胞之间 Panx1 介导的通讯回路是促进损伤后上皮再生的关键步骤。