FPF EFFECT ON MATURATION OF FETAL TYPE II CELLS

FPF 对胎儿 II 型细胞成熟的影响

• 批准号: 3351598
• 负责人: MARTIN POST
• 金额: $ 13.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351598
• 关键词: affinity chromatography; autoradiography; cell differentiation; embryo /fetus; enzyme linked immunosorbent assay; gel electrophoresis; gel filtration chromatography; gestational age; growth /development; immunoprecipitation; lung alveolus; paper chromatography; pentosyltransferase; phosphatidylcholines; phospholipase D; phosphorylation; phosphotransferases; pulmonary surfactants; spectrometry; thin layer chromatography; tissue /cell culture; transferase

The alveoli of the lung are lined with pulmonary surfactant, a lipid-rich material that lowers the surface-tension within the alveoli and there by prevents aveolar collapse. The ability of pulmonary surfactant to reduce the surface tension at end expiration is of critical importance at birth. A deficiency of pulmonary surfactant is considered to be responsible for Respiratory Distress Syndrome (RDS). RDS occurs almost exclusively in premature infants and is a major cause of neonatal death. At the end of gestation lung maturation, especially the onset of surfactant production is regulated by endogenous fetal glucocorticoids. Evidence is presented that the glucocorticoid effect on lung maturation is dependent on mesenchymal epithelial interactions. In response to glucocorticoids, the lung mesenchyme produces an oligopeptide, fibroblast pneumonocyte factor (FPF) which in turn stiumlates the formation of surfactant by alveolar Type II cells. Our goal is to determine by which mechanism FPF regulates surfactant snythesis in alveolar Type II cells from fetal lung. Initial studies will explore the effect of FPF on key enzymes involved in the synthesis de novo of surfactant associated phosphatidylcholine. We have recently identified cholinephosphate cytidylyltransferase to be the enzyme catalyzing the rate-limiting reaction in the formation of phosphatidylcholine by alveolar Type II cells. Further evaluation will include the regulatory mechanism(s) (e.g. phosphorylation-dephosphorylation, translocation) of this enzyme and its modulation, if present, by FPF. These studies should provide a better understanding in the mechanism by which lung maturation is regulated.

肺的肺泡里布满了肺表面活性物质，一种富含脂质的 降低肺泡内表面张力的物质， 防止肺泡萎陷。 肺表面活性物质降低 呼气末的表面张力在出生时至关重要。 肺表面活性物质缺乏被认为是导致 呼吸窘迫综合征（RDS）。 RDS几乎只发生在 早产儿是新生儿死亡的主要原因。 结束时 妊娠期肺成熟，特别是表面活性物质产生的开始， 由内源性胎儿糖皮质激素调节。 所提交的证据 糖皮质激素对肺成熟作用依赖于间充质 上皮相互作用 在对糖皮质激素的反应中， 间充质产生寡肽，成纤维细胞肺细胞因子（FPF） 这反过来又刺激肺泡II型表面活性剂的形成 细胞 我们的目标是确定FPF调节表面活性剂的机制 胎肺肺泡II型细胞的合成。 初步研究将 探索FPF对参与从头合成的关键酶的影响 表面活性剂相关的磷脂酰胆碱。 我们最近发现 磷酸胆碱胞苷酰转移酶是催化 肺泡巨噬细胞形成磷脂酰胆碱的限速反应 II型细胞。 进一步评价将包括监管机制 (e.g.磷酸化-去磷酸化，易位）， 其调制，如果存在的话，通过FPF。 这些研究应该提供更好的 了解肺成熟的调节机制。