The effect of HSP47 antisense to protect the pulmonary fibrosis caused by paraquat intoxication

HSP47反义蛋白对百草枯中毒所致肺纤维化的保护作用

• 批准号: 14571450
• 负责人: YAMAMOTO Hitoshi
• 金额: $ 2.24万
• 依托单位: Oita University (2003)大分医科大学 (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571450/
• 关键词: paraquat; HSP47 antisense; collagen; pulmonary fibrosis; HSP47; 肺線維化; 線維化; HSP; アンチセンス

Paraquat is a controversial and one of the most commonly used herbicides in the world. Although liver, kidney, heart and CNS are affected, lung damage resulting to pulmonary fibrosis is the usual cause of deaths in the cases with intoxication. The mechanism of paraquat toxicity is not clear but we showed the induction of heat shock protein 47(Hsp47), collagen specific molecular chaperone, related to pulmonary fibrosis. Hsp47 antisense, has beneficial effects on the treatment of fibrosis, and increased survival rate of paraquat treated rat model. The antifibrotic effect of Hsp47 antisense has shown to be due to inhibition of folding, assembly and transport of collagen fibers.

百草枯是一种有争议的除草剂，也是世界上最常用的除草剂之一。虽然肝、肾、心脏和中枢神经系统受到影响，但肺损伤导致的肺纤维化是中毒患者常见的死亡原因。百草枯的毒性机制尚不清楚，但我们发现热休克蛋白47(Hsp47)的诱导与肺纤维化有关，Hsp47是胶原特异性分子伴侣。HSP47反义核酸对肝纤维化有治疗作用，并能提高百草枯大鼠模型的存活率。Hsp47反义核酸的抗纤维化作用是由于抑制了胶原纤维的折叠、组装和运输。

项目成果

Antisene oligonucleotide inhibition of heat shock protein(HSP)47 improves bleomycin-induced pulmonary fibrosis in rats

反义寡核苷酸抑制热休克蛋白（HSP）47可改善博莱霉素诱导的大鼠肺纤维化

• 发表时间: 2007
• 期刊: Respiratory Research 8
• 作者: Satoshi Hagiwara;Hideo Iwasaka;Shigekiyo Matsumoto;Takayuki Noguchi
• 通讯作者: Takayuki Noguchi

Coexpression of HSP47 gene and type I and type III collagen genes in LPS-induced pulmonary fibrosis in rats.

• 发表时间: 2007
• 期刊: Lung
• 影响因子: 5
• 作者: S. Hagiwara;H. Iwasaka;Shigekiyo Matsumoto;T. Noguchi;H. Yoshioka