c-fos基因在内皮素-1促肺泡Ⅱ型细胞表面活性物质合成中的作用

ROLE OF c fos GENE IN THE PULMONARY SURFAC TANT SYNTHESIS OF CULTURED ALVEOLAR TYPE Ⅱ CELLS INDUCED BY ENDOTHELIN 1 *

应用反义技术探讨ｃｆｏｓ基因在ＥＴ１调控肺泡Ⅱ型细胞（ＡＴⅡ）表面活性物质（ＰＳ）合成的胞内信号转导中的作用。结果显示：（１）内皮素１（ＥＴ１）可提高ＡＴⅡ细胞的３Ｈ胆碱掺入量。（２）蛋白激酶Ｃ（ＰＫＣ）激活剂ＰＭＡ可使ＡＴⅡ细胞的３Ｈ胆碱掺入量增加，ＰＫＣ抑制剂Ｈ７可抑制ＥＴ１的促ＰＳ合成效应。（３）ＥＴ１和ＰＭＡ可显著提高Ｆｏｓ蛋白表达量。Ｈ７和ｃｆｏｓ反义寡核苷酸（ＯＤＮ）预处理可抑制ＥＴ１促Ｆｏｓ蛋白表达和促３Ｈ胆碱掺入效应。（４）ＥＴ１、正义及反义ＯＤＮ对ＡＴⅡ细胞乳酸脱氢酶（ＬＤＨ）释放量均无显著影响。结果证实：ＥＴ１可促进ＡＴⅡ的ＰＳ合成，激活ＰＫＣ上调ｃｆｏｓ基因表达是ＥＴ１促ＡＴⅡ细胞合成ＰＳ的胞内信号转导途径。

Abstract The effects of endothelin 1 (ET 1) on pulmonary surfactant(PS ) synthesis of cultured alveolar type Ⅱcells(ATⅡ) were observed. The role of c fos gene in cellular signal transduction of ET 1 was studied by antisense technology The results showed that: (1) ET 1 enhanced choline incorporation into ATⅡcells in a dose dependent manner. (2) Protein kinase (PKC) activator PMA increased choline incorporation into ATⅡ cells, while PKC inhibitor H 7 inhibited the stimulating effect of ET 1. (3) Both ET 1 and PMA could increase the level of c Fos protein, and H 7 and c fos antisense oligonucleotides (AS ODN) could inhibit the effects induced by ET 1 on Fos protein expreesion and choline incorporation. (4) The release of lactic dehydrogenase (LDH) was not different among control, ET 1, antisense oligonucleotides and sense oligonucleotides groups. The above results demonstrated that ET 1 can enhance PS synthesis of AT Ⅱcells and ET 1 stimulating the expression of c fos gene mediated by PKC is a major signal transduction pathway of modulating PS synthesis.