Keratinocyte growth factor modulates alveolar epithelial cell phenotype in vitro:: Expression of aquaporin 5
Keratinocyte growth factor modulates alveolar epithelial cell phenotype in vitro:: Expression of aquaporin 5
复制标题
DOI：
10.1165/ajrcmb.18.4.2838
复制
发表时间：
1998-04-01
影响因子：
6.4
通讯作者：
Crandall, ED
中科院分区：
文献类型：
--
作者：
Borok, Z;Lubman, RL;Crandall, ED
我们研究了角质形成细胞生长因子（KGF）在体外调节肺泡上皮细胞（AEC）表型中的作用。在原代培养的AEC中，评价KGF对细胞形态、表面活性剂载脂蛋白A、B和C（SP-A、-B和-C）表达以及水通道蛋白5（AQP 5）表达的影响，AQP 5是一种原位存在于肺泡I型（AT 1）细胞顶端表面但在肺泡II型（AT 2）细胞中不表达的水通道。从第0天（即，接种时间）或培养第4天或第6天至第8天。细胞表面生物素化研究表明，AEC单层仅在其顶端表面表达AQP 5。对照AEC在KGF缺乏下生长至第8天表达增加水平的AQP 5，与向AT 1细胞表型的转变一致。从第0天起，AEC暴露于KGF导致AQP 5表达降低，立方体形态保留，并且培养第8天相对于对照组的板层体数量更多。从第4天或第6天用KGF处理的AEC表现出AQP 5表达的减少，通过随后的几天在培养中，以及表面活性剂脱辅基蛋白的表达增加。这些数据表明，KGF既防止和逆转AQP 5（和表面活性剂载脂蛋白减少）表达的增加，伴随着AT 2向AT 1细胞表型的进展，支持的概念，AT 2和AT 1细胞表型之间的转分化至少部分是可逆的，KGF可能在调节AEC表型中发挥重要作用。
We investigated the role of keratinocyte growth factor (KGF) in regulation of alveolar epithelial cell (AEC) phenotype in vitro. Effects of KGF on cell morphology, expression of surfactant apoproteins A, B, and C (SP-A, -B, and -C), and expression of aquaporin 5 (AQP5), a water channel present in situ on the apical surface of alveolar type I (AT1) cells but not expressed in alveolar type II (AT2) cells, were evaluated in AECs grown in primary culture. Observations were made on AEC monolayers grown in serum-free medium without KGF (control) or grown continuously in the presence of KGF (10 ng/ml) from either Day 0 (i.e., the time of plating) or Day 4 or 6 through Day 8 in culture. AECs monolayers express AQP5 only on their apical surfaces as determined by cell surface biotinylation studies. Control AECs grown in the absence of KGF through Day 8 express increasing levels of AQP5, consistent with transition toward the AT1 cell phenotype. Exposure of AECs to KGF from Day 0 results in decreased AQP5 expression, retention of a cuboidal morphology, and greater numbers of lamellar bodies relative to control on Day 8 in culture. AECs treated with KGF from Day 4 or 6 exhibit a decrease in AQP5 expression through subsequent days in culture, as well as an increase in expression of surfactant apoproteins. These data, showing that KGF both prevents and reverses the increase in AQP5 (and decrease in surfactant apoprotein) expression that accompanies progression of the AT2 toward the AT1 cell phenotype, support the concepts that transdifferentiation between AT2 and AT1 cell phenotypes is at least partially reversible and that KGF may play a major role in modulating AEC phenotype.