Development of therapeutic ways on various pathological features in chronic obstructive pulmonary diseases

慢性阻塞性肺疾病多种病理特征治疗方法的进展

基本信息

批准号：
12470527
负责人：
MIYATA Takeshi
金额：
$ 8.45万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470527/
关键词：
ETS transcription factor airway mucin GM-CSF pulmonary surfactant lung epithelial cells 気道上皮細胞慢性閉塞性呼吸器疾患グリチルリチン prostanlandin E_2 11β-hydroxysteroid dehydrogenase 肺胞上皮細胞細胞分化 MEF ETS-2 漢方薬

项目摘要

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity in the world. However, there are only a few therapeutic drugs for the treatment of this disease. To evaluate new pharmacological approaches for COPD, it is necessary to make progress in understanding lung physiology and pathophysiology of COPD. The findings in this study were summarized below.1. We have found that myeloid Elf-1 like factor (MEF) regulated the differentiation of airway epithelial cells. In addition to this, MEF-transfected carcinoma cells did not grow. Therefore, we proposed that MEF act as not only a differentiation regulator, but also a tumor suppressor.2. We found that GM-CSF mRNA expression was upnregulated by ETS-2 transcription factor in adenocarcinoma cells, and was a target of protein kinase C.3. We have found some new drugs to control mucous secretion in airway diseases. Among them, fudosteine, a new cysteine derivative, inhibited the formation of airway goblet cells, and glycyrrhizin, inhibited mucus production by enhancing the effect of glucocorticoids.4. We have found new endogenous pulmonary surfactant secretagogues, adrenomedullin and prostaglandin E_2. We also found that there is a synergistic cross-talk between protein kinase A- and protein kinase C-dependent signalings in alveolar type II cells.

慢性阻塞性肺疾病（COPD）是世界范围内发病的主要原因。然而，治疗这种疾病的治疗药物却很少。为了评估治疗慢性阻塞性肺病的新药理学方法，有必要在了解慢性阻塞性肺病的肺生理学和病理生理学方面取得进展。本研究的结果总结如下： 1．我们发现髓样Elf-1样因子（MEF）调节气道上皮细胞的分化。除此之外，MEF 转染的癌细胞不生长。因此，我们提出MEF不仅具有分化调节因子的作用，而且具有肿瘤抑制因子的作用。 2．我们发现腺癌细胞中 GM-CSF mRNA 表达被 ETS-2 转录因子上调，并且是蛋白激酶 C.3 的靶标。我们发现了一些控制气道疾病粘液分泌的新药。其中，新的半胱氨酸衍生物福多司坦抑制气道杯状细胞的形成，甘草酸通过增强糖皮质激素的作用抑制粘液产生。 4．我们发现了新的内源性肺表面活性物质促分泌素、肾上腺髓质素和前列腺素E_2。我们还发现 II 型肺泡细胞中蛋白激酶 A 和蛋白激酶 C 依赖性信号传导之间存在协同串扰。