Foster Cherie D, Varghese Linda S, Skalina Rachel B, Gonzales Linda W, Guttentag Susan H
Department of Pediatrics, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Pediatr Res. 2007 Apr;61(4):404-9. doi: 10.1203/pdr.0b013e3180332c6d.
For alveolar type I cells, phenotype plasticity and physiology other than gas exchange await further clarification due to in vitro study difficulties in isolating and maintaining type I cells in primary culture. Using an established in vitro model of human fetal type II cells, in which the type II phenotype is induced and maintained by adding hormones, we assessed for transdifferentiation in culture toward a type I-like cell with hormone removal for up to 144 h, followed by electron microscopy, permeability studies, and RNA and protein analysis. Hormone withdrawal resulted in diminished type II cell characteristics, including decreased microvilli, lamellar bodies, and type II cell marker RNA and protein. There was a simultaneous increase in type I characteristics, including increased epithelial cell barrier function indicative of a tight monolayer and increased type I cell marker RNA and protein. Our results indicate that hormone removal from cultured human fetal type II cells results in transdifferentiation toward a type I-like cell. This model will be useful for continued in vitro studies of human fetal alveolar epithelial cell differentiation and phenotype plasticity.
由于在原代培养中分离和维持I型细胞存在体外研究困难，I型肺泡细胞除气体交换外的表型可塑性和生理学仍有待进一步阐明。利用已建立的人胎儿II型细胞体外模型，通过添加激素诱导并维持II型细胞表型，我们评估了在去除激素长达144小时的培养过程中向I型样细胞的转分化情况，随后进行电子显微镜检查、通透性研究以及RNA和蛋白质分析。去除激素导致II型细胞特征减弱，包括微绒毛、板层小体减少，以及II型细胞标志物RNA和蛋白质减少。同时，I型细胞特征增加，包括上皮细胞屏障功能增强，表明形成紧密单层，以及I型细胞标志物RNA和蛋白质增加。我们的结果表明，从培养的人胎儿II型细胞中去除激素会导致向I型样细胞的转分化。该模型将有助于继续进行人胎儿肺泡上皮细胞分化和表型可塑性的体外研究。
