Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF.
Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF.
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DOI：
10.1152/ajpcell.2001.281.4.c1291
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发表时间：
2001-10
期刊：
影响因子：
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通讯作者：
B. Isakson;R. Lubman;G. Seedorf;S. Boitano
中科院分区：
文献类型：
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作者：
B. Isakson;R. Lubman;G. Seedorf;S. Boitano
肺泡上皮由两种细胞类型组成，肺泡I型（AT 1）和肺泡II型（AT 2）细胞。我们最近发现，在I型胶原/纤连蛋白基质上生长的7天龄AT 2细胞培养物形成了AT 1细胞的表型特征，显示出独特的连接蛋白谱，并通过间隙连接协调机械诱导的细胞间Ca（2+）变化（25）。在这项研究中，我们培养AT 2细胞7天的基质补充层粘连蛋白-5和/或角质形成细胞生长因子的存在下。在这些条件下，培养的AT 2细胞显示AT 2型形态，表达AT 2特异性标志物表面活性蛋白C，不表达AT 1特异性细胞标志物水通道蛋白5，所有这些都与维持AT 2表型一致。这些AT 2样细胞也协调机械诱导的细胞间Ca（2+）信号传导，但与AT 1样细胞不同，它是通过细胞外核苷酸三磷酸的释放来实现的。此外，保留AT 2细胞特异性标志物的培养细胞表达与具有AT 1特征的培养细胞不同的连接蛋白谱。细胞间Ca（2+）信号的变化与细胞分化的平行关系提示细胞信号传导机制是肺泡细胞表型的内在组成部分。由于肺上皮损伤伴随细胞外基质和生长因子的变化，随后是广泛的细胞分裂，分化和迁移的AT 2祖细胞，我们认为，类似的变化可能是至关重要的肺恢复和修复过程中体内。
The alveolar epithelium consists of two cell types, alveolar type I (AT1) and alveolar type II (AT2) cells. We have recently shown that 7-day-old cultures of AT2 cells grown on a type I collagen/fibronectin matrix develop phenotypic characteristics of AT1 cells, display a distinct connexin profile, and coordinate mechanically induced intercellular Ca(2+) changes via gap junctions (25). In this study, we cultured AT2 cells for 7 days on matrix supplemented with laminin-5 and/or in the presence of keratinocyte growth factor. Under these conditions, cultured AT2 cells display AT2 type morphology, express the AT2-specific marker surfactant protein C, and do not express AT1-specific cell marker aquaporin 5, all consistent with maintenance of AT2 phenotype. These AT2-like cells also coordinate mechanically induced intercellular Ca(2+) signaling, but, unlike AT1-like cells, do so by using extracellular nucleotide triphosphate release. Additionally, cultured cells that retain AT2 cell-specific markers express connexin profiles different from cultured cells with AT1 characteristics. The parallel changes in intercellular Ca(2+) signaling with cell differentiation suggest that cell signaling mechanisms are an intrinsic component of lung alveolar cell phenotype. Because lung epithelial injury is accompanied by extracellular matrix and growth factor changes, followed by extensive cell division, differentiation, and migration of AT2 progenitor cells, we suggest that similar changes may be vital to the lung recovery and repair process in vivo.