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

本研究利用博莱霉素处理的小鼠、长期香烟烟雾暴露的小鼠和高表达肿瘤坏死因子-α的肺纤维化转基因小鼠，研究了胶原特异性分子伴侣HSP47在肺气肿和肺纤维化中的表达和调控。博莱霉素处理的小鼠肺组织羟脯氨酸含量从给药后4周开始增加，12周达到最大。与对照组相比，HSP47基因表达在治疗后4周和5周有一过性升高，但在12周时表达增加。而长期香烟烟雾暴露小鼠肺组织HSP47基因与对照组相比，差异无统计学意义(P>0.05)。转基因小鼠在5个月龄时出现HSP47基因抑制，1岁时与同龄非转基因小鼠相比也有这种趋势。肺功能、肺纤维化程度和肺组织羟脯氨酸含量在4~5个月龄时也达到最大值，此后一直维持到1岁以上。TG小鼠IV型胶原基因表达与HSP47基因表达平行，而不是I型和III型胶原基因表达。Tg组小鼠肺泡灌洗液中的总弹力略高于非Tg组，而MMP1基因在1~4个月龄时表达。上述结果提示，HSP47基因可能与不可逆性肺纤维化的进展有关，但不是纤维化的触发因素。然而，在实验模型中，我们不能明确HSP47基因与肺气肿的关系。HSP47基因调控可调节进行性肺纤维化中胶原的沉积。

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.