In vivo transfer of an extracellular domain of platelet-derived growth factor beta gene by HVJ-liposome method ameliorated bleomycin-induced pulmonary fibrosis.

通过 HVJ 脂质体方法体内转移血小板源性生长因子 β 基因的细胞外结构域可改善博莱霉素诱导的肺纤维化。

• 批准号: 08457181
• 负责人: HAYASHI Seiji
• 金额: $ 2.24万
• 依托单位: OSAKA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457181/
• 关键词: HVJ-liposome; Pulmonary Fibrosis; In vivo gene transfer; platelet-derived growth factor; platelet-derived growth factor receptor; bleomycin; 間質性肺炎; サイトカイン; PDGF; 可溶性PDGF受容体; TGF-β

Platelet-derived growth factor (PDGF) is one of the most potent mitogens and chemoattractants for a variety of mesenchymal cells. A number of investigators have reported augmented expression of PDGF in the lung with IPF and other pulmonary fibrosis. To accomplish regulation of PDGF activity, we constructed an expression plasmid of the extracellular domain of PDGF receptor beta chain (XR), which lacks intracellular tyrosine kinase domain and transmembrane portions, and we estimated the therapeutic effects of the XR gene transfer through trachea on bleomycin-induced lung fibrosis of C57BL/6 mice by using hemagglutinating virus of Japan (HVJ)-liposome method. The transfer of the XR gene improved the increase in the wet weight, hydroxyproline content and histopathologic change of the lung that was induced by bleomycin. These findings suggested that PDGF playd a crucial role in the pathogenesis of pulmonary fibrosis, and the XR gene by using the HVJ-liposome method may limit the progression of pulmonary fibrosis.

血小板源性生长因子（PDGF）是一种最有效的有丝分裂原和各种间充质细胞的化学引诱剂。许多研究者报告了IPF和其他肺纤维化患者肺中PDGF表达增加。为了实现PDGF活性的调控，我们构建了PDGF受体β链（XR）胞外区的表达质粒，该表达质粒缺乏胞内酪氨酸激酶区和跨膜区，并采用日本血凝病毒（HVJ）-脂质体法评价了经气管导入XR基因对博莱霉素诱导的C57 BL/6小鼠肺纤维化的治疗作用。XR基因的转染改善了博莱霉素引起的肺湿重、羟脯氨酸含量的增加和肺组织病理学改变。提示PDGF在肺纤维化的发病机制中起重要作用，利用HVJ-脂质体法转染XR基因可能限制肺纤维化的进展。

项目成果

Bidwell, M., et al.: "Analysis of messenger ribonucleic acid and protein for the ligands and receptors of the platelet-derived growth factor signaling pathway in the placenta, extraembryonic membranes, and uterus during the latter half of murine gestation

Bidwell, M. 等人：“小鼠妊娠后半期胎盘、胚外膜和子宫中血小板衍生生长因子信号通路配体和受体的信使核糖核酸和蛋白质分析

林清二 他: "気道肺胞上皮細胞へのin vivo遺伝子導入-間質性肺炎の病態解析" 医学のあゆみ. 176. 677-681 (1996)

Seiji Hayashi 等人：“体内基因转移至气道肺泡上皮细胞 - 间质性肺炎的病理分析”，医学史 176. 677-681 (1996)。

Woessner, J.F., at al: "The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid.Arch.Biochemical." Biophys. 93. 440-447 (1961)

Woessner, J.F. 等人：“含有少量这种亚氨基酸的组织和蛋白质样品中羟脯氨酸的测定。Arch.Biochemical。”

吉田光宏、林清二: "生体内遺伝子導入によるTGF-βおよびPDGFの肺線維症における病態解析" 日本臨床. 54. 418-422 (1996)

Mitsuhiro Yoshida、Seiji Hayashi：“通过体内基因转移对肺纤维化中的 TGF-β 和 PDGF 进行病理学分析”，日本临床，54. 418-422 (1996)。

林 清二: "TGF-β" KEY WORD 1996-‘97 呼吸器系. 150-151 (1996)

Seiji Hayashi：“TGF-β”关键词 1996-97 呼吸系统。