Pre- and postnatal lung development, maturation, and plasticity - Insulin-like growth factor I receptor is downregulated after alveolarization in an apoptotic fibroblast subset
Pre- and postnatal lung development, maturation, and plasticity - Insulin-like growth factor I receptor is downregulated after alveolarization in an apoptotic fibroblast subset
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DOI：
10.1152/ajplung.00050.2001
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发表时间：
2002-03-01
影响因子：
4.9
通讯作者：
Bruce, MC
中科院分区：
文献类型：
--
作者：
Srinivasan, S;Strange, J;Bruce, MC
肺泡形成后，>20%的间质性肺成纤维细胞经历凋亡，这是一个对正常肺成熟至关重要的过程。未成熟的肺包含两种形态上不同的成纤维细胞群，脂质填充的间质成纤维细胞（LIF）和非LIF（NLIF），其在收缩蛋白含量、增殖能力和纤连蛋白和I型和III型胶原mRNA表达方面不同，但弹性蛋白原不相同。肺泡化后，凋亡只发生在一个成纤维细胞群，LIF。使用流式细胞术分析用亲脂性荧光染料染色的成纤维细胞，我们确定了一个子集，命名为LIF（-），含有较少的脂滴。与保留脂质的LIF不同，LIF（+），LIF（-）在肺泡化后不经历凋亡。在LIF（+）中，凋亡与胰岛素样生长因子I受体（IGF-IR）mRNA和细胞表面蛋白表达的下调相关。抗IGF-IR治疗降低了总肺成纤维细胞存活率（P=0.05），磷脂酰肌醇3-激酶抑制剂LY-294002和ras-raf-丝裂原活化蛋白激酶抑制剂PD-98059治疗也是如此（P
After alveolar formation, >20% of interstitial lung fibroblasts undergo apoptosis, a process that is of critical importance for normal lung maturation. The immature lung contains two morphologically distinct fibroblast populations, lipid-filled interstitial fibroblasts (LIF) and non-LIF (NLIF), which differ with respect to contractile protein content, proliferative capacity, and expression of mRNAs for fibronectin and types I and III collagen, but not tropoelastin. After alveolarization, apoptosis occurs in only one fibroblast population, the LIF. Using flow cytometry to analyze fibroblasts stained with a lipophilic, fluorescent dye, we identified a subset, designated LIF(-), that contained fewer lipid droplets. Unlike LIF that retain lipid, LIF(+), the LIF(-) do not undergo apoptosis after alveolarization. In LIF(+), apoptosis was correlated with downregulation of insulin-like growth factor I receptor (IGF-IR) mRNA and cell surface protein expression. Treatment with anti-IGF-IR decreased total lung fibroblast survival (P=0.05) as did treatment with the phosphatidylinositol 3-kinase inhibitor LY-294002 and the ras-raf-mitogen-activated protein kinase inhibitor PD-98059 (P