权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

EXPRESSION AND REGULATION OF COLLAGEN SPECIFIC MOLECULAR CHAPERONE HSP47 IN PULMONARY EMPHYSEMA AND FIBROSIS

胶原蛋白特异性分子伴侣 HSP47 在肺气肿和纤维化中的表达和调节

基本信息

批准号：
08670682
负责人：
ISHIHARA Yoko
金额：
$ 1.47万
依托单位：
TOKYO WOMEN'S MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

This work was investigated the expression and regulation of collagen specific molecular chaperone HSP47 in pulmonary emphysema and fibrosis, using bleomycin-treated mice, long term cigarette smoke-exposed mice and TNF-alpha overexpression pulmonary-fibrosis transgenic (Tg) mice.Bleomycin-treated mice showed increase of lung hydroxyproline contents from week 4, and reached to a maximum at week 12 after administration. HSP47 gene expression was increased a transient at week 4 and 5 after treatment, but at week 12, compared with the control group. On the other hand, lung HSP47 gene did not show any marked changes during long term cigarette smoke-exposed mice (from day 4 to month 12) compared with the control group. Tg mice showed HSP47 gene suppression at 5 mo of age, this tendency was also observed at 1 year of age compared with same age of non-Tg mice. Pulmonary function pattern, the degree of fibrotic lesion in morphological findings, and lung hydroxyproline contents also reached to a maximum at 4-5 mo of age, and then this levels were maintained until over 1 year of age. Collagen typ IV gene expression in Tg mice paralleled HSP47 gene expression rather than collagen type (I) and (III). Total elastolytic activity in bronchoalveolar lavage showed a slight increase, whereas MMP-1 gene was expressed at from 1 to 4 mo of age in Tg mice compared with the non-Tg group. TGF-beta gene over expression was not observed during experimental period in the Tg mice.Above results suggest that HSP47 gene may be related to the progressive of non-reversible pulmonary fibrosis, but not as a trigger of fibrosis. However, we could not define the relationship between HSP47 gene and pulmonary emphysema in the experiment model. Collergen deposition could be regulated by control of HSP47 gene in the progressive pulmonary fibrosis.

本研究采用博莱霉素处理小鼠、长期暴露于香烟烟雾中的小鼠和tnf - α过表达肺纤维化转基因（Tg）小鼠，研究了胶原特异性分子伴侣HSP47在肺气肿和纤维化中的表达和调控。博莱霉素处理小鼠肺羟脯氨酸含量从第4周开始增加，并在给药后第12周达到最大值。与对照组相比，HSP47基因表达在治疗后第4周和第5周短暂升高，但在第12周。另一方面，与对照组相比，长期吸烟小鼠（从第4天到第12个月）肺部HSP47基因没有表现出任何明显的变化。Tg小鼠在5月龄时表现出HSP47基因抑制，与非Tg小鼠相比，1岁时也表现出这种趋势。肺功能模式、形态学表现的纤维化程度、肺羟脯氨酸含量在4 ~ 5月龄时达到最大值，此后一直维持到1岁以上。Tg小鼠中胶原IV型基因表达与HSP47基因表达平行，而与胶原I型和III型基因表达平行。与非Tg组相比，Tg小鼠支气管肺泡灌洗的总弹性溶解活性略有增加，而MMP-1基因在1至4月龄时表达。实验期间Tg小鼠未见tgf - β基因过表达。以上结果提示，HSP47基因可能与非可逆性肺纤维化的进展有关，但不是纤维化的触发因素。但在实验模型中，我们无法明确HSP47基因与肺气肿的关系。HSP47基因的表达可调控进行性肺纤维化中胶原蛋白的沉积。