The Rho Pathway Mediates Transition to an Alveolar Type I Cell Phenotype During Static Stretch of Alveolar Type II Cells
The Rho Pathway Mediates Transition to an Alveolar Type I Cell Phenotype During Static Stretch of Alveolar Type II Cells
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DOI：
10.1203/pdr.0b013e3181dbc708
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发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Guttentag, Susan H.
中科院分区：
文献类型：
--
作者：
Foster, Cherie D.;Varghese, Linda S.;Guttentag, Susan H.
伸展是肺生长和发育的重要机制。其中胎肺已被长期过度或欠膨胀的动物模型表明，II型和I型细胞的破坏混合，静态过度膨胀通常促进I型细胞表型。已知Rho GT3家族是细胞骨架信号传导的关键调节因子，其介导细胞分化以响应其他器官中的拉伸。使用一个良好的肺泡上皮细胞分化模型和一个有效的拉伸装置，我们研究了超生理拉伸对人胎肺肺泡上皮细胞表型的影响。如预测的那样，施加于上皮细胞的静态拉伸抑制II型细胞标志物（SP-B和胃蛋白酶原C，PGC），并诱导I型细胞标志物（小窝蛋白-1，Claudin 7和纤溶酶原激活物抑制剂-1，派-1）。静态牵张也与Rho A激活相关。此外，Rho激酶抑制剂Y27632降低了Rho A的激活，并减弱了牵张诱导的肺泡上皮细胞标志物表达的变化。总之，这些数据提供了进一步的证据，细胞骨架的机械刺激和Rho激活是机械转导相关的肺泡上皮细胞分化的关键上游事件。（儿科研究67：585-590，2010）
Stretch is an essential mechanism for lung growth and development. Animal models in which fetal lungs have been chronically over or underdistended demonstrate a disrupted mix of type II and type I cells, with static overdistention typically promoting a type I cell phenotype. The Rho GTPase family, key regulators of cytoskeletal signaling, are known to mediate cellular differentiation in response to stretch in other organs. Using a well-described model of alveolar epithelial cell differentiation and a validated stretch device, we investigated the effects of supraphysiologic stretch on human fetal lung alveolar epithelial cell phenotype. Static stretch applied to epithelial cells suppressed type II cell markers (SP-B and Pepsinogen C, PGC), and induced type I cell markers (Caveolin-1, Claudin 7 and Plasminogen Activator Inhibitor-1, PAI-1) as predicted. Static stretch was also associated with Rho A activation. Furthermore, the Rho kinase inhibitor Y27632 decreased Rho A activation and blunted the stretch-induced changes in alveolar epithelial cell marker expression. Together these data provide further evidence that mechanical stimulation of the cytoskeleton and Rho activation are key upstream events in mechanotransduction-associated alveolar epithelial cell differentiation. (Pediatr Res 67: 585-590, 2010)