EXTRACELLULAR MATRIX AND THE CONTROL OF FETAL LUNG EPITHELIAL CELL GROWTH

细胞外基质与胎儿肺上皮细胞生长的控制

• 批准号: 3843556
• 负责人: MICHAEL A HARALSON
• 金额: --
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3843556
• 关键词: alkaline phosphatase; cell differentiation; clone cells; collagen; dexamethasone; enzyme activity; epidermal growth factor; extracellular matrix; lysozyme; phase contrast microscopy; phosphatidylcholines; phospholipids; proteins; pulmonary surfactants; respiratory epithelium; retinoate; surfactant; transforming growth factors; transmission electron microscopy

The growth and maturation of the type II alveolar epithelial cell plays a key role in fetal lung development. Not only have several growth factors and hormones (EGF, retinoic acid, glucocorticoids and TGF-beta) been documented to impact upon the functional differentiation of the type II pneumocyte, the extracellular matrix (ECM) has also been demonstrated to profoundly influence the functional properties of this cell type. furthermore, the same recognized mediators of type II cell differentiation are also known regulators of ECM production. It is the hypothesis of this proposal that an interrelationship exists between soluble mediators and matrix biosynthesis, and that the former factors influence, at least in part, the functional properties of the type II alveolar epithelial cell by affecting the matrix phenotype of this cell. To test this hypothesis, we have been examining the effects of EGF, retinoic acid and TGF-beta and different matrices (type I collagen and matrigel) on the growth, culture morphology and collagen production in a possible cell culture model (FRLE cells) of the fetal type II pneumocyte. It is the purpose of this proposal to extend our observations to examine the effects of these soluble factors, as well as dexamethasone, and different matrices on the expression of differentiated functions (disaturated phosphatidylcholine and SP-A synthesis, expression of alkaline phosphatase and lysozyme, production of cell surface lectins (Maclura pomifera agglutinin (MPA) and Ricinus communis I (RCI) lectin), and collagen biosynthesis) by FRLE cells, to partially identify the matrix components responsible for expression of these differentiated functions, and to establish the effects of matrix on the response of FRLE cells to these soluble factors. These studies should provide further insight into the nature of FRLE cells, the mechanisms of cell-matrix interactions and the possible mediators of type II cell development under normal and pathological conditions.

Ⅱ型肺泡上皮细胞的生长和成熟对肺泡上皮细胞的增殖和分化起着重要作用。 在胎儿肺发育中的关键作用。 不仅有几个增长因素 和激素（EGF，视黄酸，糖皮质激素和TGF-β） 记录影响II型糖尿病的功能分化 细胞外基质（ECM）也已被证明 深刻地影响了这种细胞类型的功能特性。 此外，同样公认的II型细胞分化介质 也是ECM产生的已知调节剂。 这是一个假设 建议可溶性介质之间存在相互关系， 基质生物合成，以及前因素的影响，至少在 部分，II型肺泡上皮细胞的功能特性， 影响该细胞的基质表型。 为了验证这个假设，我们 一直在研究EGF、维甲酸和TGF-β的作用， 不同基质（I型胶原和基质胶）对生长、培养 在可能的细胞培养模型（FRLE）中的形态和胶原蛋白产生 胎儿II型肺细胞。 这是这个提议的目的 为了扩展我们的观察以检查这些可溶性因子的影响， 以及地塞米松，以及不同基质对 分化功能（二饱和磷脂酰胆碱和SP-A 碱性磷酸酶和溶菌酶的合成、表达、 细胞表面凝集素（Maclura pomifera凝集素（MPA）和蓖麻凝集素（Ricinus communis I（RCI）凝集素）和胶原蛋白生物合成）， 部分识别负责表达的基质组分 这些差异化的功能，并建立矩阵的影响， FRLE细胞对这些可溶性因子的反应。 这些研究应 提供进一步了解FRLE细胞的性质， 细胞-基质相互作用和II型细胞的可能介质 在正常和病理条件下的发展。