Role of glycosphingolipids in lung cells

鞘糖脂在肺细胞中的作用

• 批准号: 21K08165
• 负责人: 小池 建吾
• 金额: $ 2.66万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K08165/
• 关键词: スフィンゴ糖脂質; 慢性閉塞性肺疾患; 喫煙

慢性閉塞性肺疾患（chronic obstructive pulmonary disease: COPD）は、タバコ煙を主とする有害物質を長期に吸入曝露することで発症する難治性疾患である。細胞膜の脂質二重層を構成するスフィンゴ脂質は、膜の構造維持に貢献し、増殖・分化・アポトーシスなど多彩な細胞機能に関与するため、様々な疾患の病態生理に関わることが明らかになりつつある。スフィンゴ糖脂質の一つであるGlucosylceramide（GlcCer）が、タバコ煙曝露下での肺血管内皮細胞の生存に必須である事を我々は報告したが、いまだにその他の肺細胞での働きは不明であり、GlcCerの下流のリン脂質のタバコ煙曝露下での役割も不明である。そこで、GlcCerの血管内皮細胞以外の肺細胞での役割やGlcCer以外のCOPD病態生理に関わるスフィンゴ糖脂質の発見を目的として実験計画を立案した。In vitroの実験系で、Glucosylceramide産生酵素（Glucosylceramide synthase: GCS）のヒト肺気道上皮細胞での役割について調査したところ、血管内皮細胞と同様に喫煙曝露抽出液曝露あるいはGCS阻害薬によって、肺気道上皮細胞のオートファジーの機能不全やアポトーシスが生じることを認めた。また、GlcCer以外のスフィンゴ糖脂質もCOPD患者の血清で有意に変化していたことから、In vivoの実験系として野生型マウスに喫煙曝露を行い、肺組織での酵素のmRNAをリアルタイムPCRで測定した。その結果、1ヵ月曝露の肺検体にてスフィンゴ糖脂質に関連する複数の酵素のmRNA減少傾向を認めたが、3カ月曝露の肺検体ではLactosylceramide産生酵素より下流の一部の酵素でmRNAの増加傾向を認めた。

Chronic obstructive pulmonary disease (chronic obstructive pulmonary disease: COPD), chronic obstructive pulmonary disease (COPD) and chronic obstructive pulmonary disease (COPD). The cell membrane fat is double-linked, the membrane fat is preserved, the membrane is maintained, and the cellular machinery of the multicolor cell is able to communicate with the disease, the disease and the disease. As soon as the glycolipids were exposed to Glucosylceramide (GlcCer), the vascular endothelial cells of the lungs were exposed that it was necessary for the survival of the vascular endothelial cells of the lung. Outside the vascular endothelial cells of GlcCer and COPD, the pathological physiology of COPD was excised and excised outside of COPD. In vitro and Glucosylceramide enzymes (Glucosylceramide synthase: GCS) were used to excise the epithelial cells of the lung, and the extractions of the endothelial cells were exposed to the extract of the same cells. The cells of the lung were blocked by GCS, and the epithelial cells of the lungs could not be completely isolated from the lung. The sera of patients with glycolipid (COPD) who were infected with glycolipids (other than GlcCer) were detected by Elisa. The sera of patients with glycolipid (COPD) were detected by enzyme mRNA enzyme assay (Elisa), lung tissue enzyme assay (PCR assay), and lung tissue test. The results were as follows: one month after exposure, the lung tissue was exposed to glycolipid, the complex number of enzymes mRNA was reduced to the lung cancer, and the lung tissue was exposed in the third month, and the enzyme mRNA was added to the recognition.