Fetal macrophages assist in the repair of ruptured amnion through the induction of epithelial-mesenchymal transition
Fetal macrophages assist in the repair of ruptured amnion through the induction of epithelial-mesenchymal transition
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DOI：
10.1126/scisignal.abi5453
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发表时间：
2022-09
影响因子：
7.3
通讯作者：
Y. Kawamura;Haruta Mogami;Eriko Yasuda;M. Takakura;Yuriko Matsuzaka;Y. Ueda;Asako Inohaya;K. Kawasaki;Yoshitsugu Chigusa;Masaki Mandai;E. Kondoh
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文献类型：
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作者：
Y. Kawamura;Haruta Mogami;Eriko Yasuda;M. Takakura;Yuriko Matsuzaka;Y. Ueda;Asako Inohaya;K. Kawasaki;Yoshitsugu Chigusa;Masaki Mandai;E. Kondoh
羊膜囊过早破裂，称为早产胎膜早破（pPROM），是早产的主要原因。在某些情况下，这些破裂的胎膜会自行愈合。在这里，我们研究了羊膜的修复机制，羊膜是羊膜囊中最接近胚胎的一层上皮细胞。巨噬细胞迁移并驻留在人和小鼠羊膜的破裂部位。在破裂部位观察到一种称为上皮间质转化（EMT）的过程，其中上皮细胞获得间质表型，并且与组织修复有关。在怀有巨噬细胞耗尽胎儿的母鼠中，羊膜破裂的修复受到损害，并且在破裂部位很少检测到 EMT。在伤口愈合试验中培养的羊膜上皮细胞的迁移是由 EMT 通过转化生长因子-β (TGF-β)-Smad 信号转导介导的。这些发现表明胎儿巨噬细胞在羊膜修复中至关重要，因为它们能够诱导羊膜上皮细胞发生 EMT。描述 羊膜囊破裂的修复可能涉及胎儿巨噬细胞引发的 EMT。胎儿巨噬细胞的救援包围胎儿的羊膜囊过早破裂可能会引发早产。由于羊膜囊可能会重新密封，Kawamura 等人。研究了羊膜囊最内层上皮细胞层（称为羊膜）的修复机制。作者发现，巨噬细胞被招募到人类和小鼠羊膜的破裂部位，显示出上皮间质转化（EMT）的迹象，这一过程赋予上皮细胞间质属性，对组织修复至关重要。妊娠小鼠胎儿巨噬细胞的消耗阻止了巨噬细胞的募集、EMT 和羊膜破裂的修复。因此，胎儿巨噬细胞在羊膜破裂部位周围的上皮细胞中诱导 EMT，以促进修复。
The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the embryo. Macrophages migrated to and resided at rupture sites in both human and mouse amnion. A process called epithelial-mesenchymal transition (EMT), in which epithelial cells acquire a mesenchymal phenotype and which is implicated in tissue repair, was observed at rupture sites. In dams bearing macrophage-depleted fetuses, the repair of amnion ruptures was compromised, and EMT was rarely detected at rupture sites. The migration of cultured amnion epithelial cells in wound healing assays was mediated by EMT through transforming growth factor–β (TGF-β)–Smad signaling. These findings suggest that fetal macrophages are crucial in amnion repair because of their ability to induce EMT in amnion epithelial cells. Description Repairs to ruptures in the amniotic sac may involve EMT elicited by fetal macrophages. Fetal macrophages to the rescue Premature rupture of the amniotic sac, which encloses the fetus, may trigger preterm birth. Because the amniotic sac may reseal, Kawamura et al. investigated repair mechanisms in the innermost epithelial cell layer of the amniotic sac, known as the amnion. The authors found that macrophages were recruited to rupture sites in human and mouse amnion, which showed signs of epithelial-mesenchymal transition (EMT), a process that confers mesenchymal attributes to epithelial cells and that is critical for tissue repair. Depletion of macrophages in fetuses in pregnant mice prevented macrophage recruitment, EMT, and repair of amnion ruptures. Thus, fetal macrophages induce EMT in the epithelial cells surrounding rupture sites in the amnion to facilitate repair.