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Mechanical stretch triggers rapid epithelial cell division through Piezo1

机译：机械拉伸通过Piezo1触发快速上皮细胞分裂

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Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die(1). However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state. Here we show that mammalian epithelial cell division occurs in regions of low cell density where cells are stretched. By experimentally stretching epithelia, we find that mechanical stretch itself rapidly stimulates cell division through activation of the Piezo1 channel. To stimulate cell division, stretch triggers cells that are paused in early G2 phase to activate calcium-dependent phosphorylation of ERK1/2, thereby activating the cyclin B transcription that is necessary to drive cells into mitosis. Although both epithelial cell division and cell extrusion require Piezo1 at the steady state, the type of mechanical force controls the outcome: stretch induces cell division, whereas crowding induces extrusion. How Piezo1-dependent calcium transients activate two opposing processes may depend on where and how Piezo1 is activated, as it accumulates in different subcellular sites with increasing cell density. In sparse epithelial regions in which cells divide, Piezo1 localizes to the plasma membrane and cytoplasm, whereas in dense regions in which cells extrude, it forms large cytoplasmic aggregates. Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion and apoptosis in crowded regions and cell division in sparse regions.
机译：尽管上皮细胞对它们所包围的器官起了屏障的作用，但它们以人体中某些最快的速度翻转。然而，上皮细胞分裂必须与细胞死亡紧密联系，以保持屏障功能并防止肿瘤形成。即将死亡的细胞数量如何与那些分裂后的细胞数量保持不变？当上皮细胞变得过于拥挤时，它们会激活拉伸激活的通道Piezo1以触发随后死亡的细胞挤出（1）。但是，尚不清楚如何控制上皮细胞分裂以平衡稳态下的细胞死亡。在这里，我们显示哺乳动物上皮细胞分裂发生在细胞被拉伸的低细胞密度区域。通过实验拉伸上皮细胞，我们发现机械拉伸本身通过激活Piezo1通道迅速刺激细胞分裂。为了刺激细胞分裂，伸展运动触发了在G2期早期停顿的细胞，以激活ERK1 / 2的钙依赖性磷酸化，从而激活驱动细胞进入有丝分裂所必需的细胞周期蛋白B转录。尽管上皮细胞分裂和细胞挤出均需要处于稳态的Piezo1，但机械力的类型控制结果：拉伸诱导细胞分裂，而拥挤诱导挤出。 Piezo1依赖性钙瞬变如何激活两个相反的过程可能取决于Piezo1在何处以及如何被激活，因为它随着细胞密度的增加而积累在不同的亚细胞部位。在细胞分裂的稀疏上皮区域中，Piezo1定位于质膜和细胞质，而在细胞挤出的密集区域中，Piezo1形成大的细胞质聚集体。由于Piezo1既感知机械拥挤又感知机械拉伸，因​​此它可以作为稳态传感器来控制上皮细胞数量，触发拥挤区域的挤出和凋亡以及稀疏区域的细胞分裂。

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  • 来源
    《Nature》 |2017年第7643期|118-121|共4页
  • 作者

    Gudipaty S. A.; Lindblom J.; Loftus P. D.; Redd M. J.; Edes K.; Davey C. F.; Krishnegowda V.; Rosenblatt J.;

  • 作者单位

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

    Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84102 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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