Expression of a calmodulin inhibitor peptide in progenitor alveolar type II cells disrupts lung development.
Expression of a calmodulin inhibitor peptide in progenitor alveolar type II cells disrupts lung development.
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II 型肺泡祖细胞中钙调蛋白抑制肽的表达会破坏肺发育。
DOI：
10.1152/ajplung.1996.271.2.l245
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Dedman,JR
中科院分区：
文献类型：
--
作者：
Wang,J;Campos,B;Kaetzel,MA;Dedman,JR
钙调素（CaM）是一种主要的细胞内钙离子介导蛋白，参与细胞的生长和分化。为了评估钙调素在肺中的功能，有必要构建编码高亲和力钙调素结合肽的基因，因为化学合成的钙调素抑制剂缺乏结合和靶向特异性。使用人表面活性蛋白C启动子将该钙调蛋白抑制肽基因靶向于转基因小鼠中的II型上皮细胞。在祖细胞II型上皮肺细胞中钙调蛋白功能的中和改变上皮细胞的生长和分化，从而阻止支气管树的分支形态发生。新生的转基因动物有未发育的肺。这项研究表明，II型肺上皮细胞需要功能性钙调素的增殖和发展。将特异性抑制剂肽靶向单一肺细胞类型是评估钙调蛋白（普遍存在的钙依赖性调节蛋白）在肺发育和疾病中的作用的方法。
Calmodulin (CaM) is a major intracellular Ca2+ mediator protein involved in cell growth and differentiation. To evaluate calmodulin function in lung, it was necessary to construct a gene that encodes a high-affinity calmodulin binding peptide, since chemically synthesized calmodulin inhibitors lack binding and targeting specificity. This calmodulin inhibitor peptide gene was targeted to type II epithelial cells in transgenic mice using the human surfactant protein C promoter. Neutralization of calmodulin function in progenitor type II epithelial pneumocytes alters epithelial cell growth and differentiation, which prevents branching morphogenesis of the bronchial tree. Newborn transgenic animals have undeveloped lungs. This study indicates that type II lung epithelial cells require functional CaM for proliferation and development. The targeting of specific inhibitor peptides to a single lung cell type is an approach to evaluate the role of calmodulin, the ubiquitous calcium-dependent regulator protein, in lung development and disease.