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

本研究采用博莱霉素治疗小鼠、长期吸烟小鼠和TNF-α过表达肺纤维化转基因小鼠，观察肺气肿和肺纤维化中胶原特异性分子伴侣HSP 47的表达和调控。与对照组相比，HSP 47基因表达在治疗后4周和5周短暂增加，但在12周时增加。长期吸烟组小鼠肺组织HSP 47基因表达与对照组相比无明显变化。Tg小鼠在5月龄时HSP 47基因表达受到抑制，与非Tg小鼠相比，在1岁时HSP 47基因表达受到抑制。肺功能、肺组织形态学纤维化程度和肺羟脯氨酸含量也在4-5月龄达到最高值，此后一直维持到1岁以上。Tg小鼠中IV型胶原基因表达高于HSP 47基因表达，而不是（I）和（III）型胶原。支气管肺泡灌洗液中的总弹性蛋白溶解活性略有增加，而MMP-1基因在1至4月龄的Tg小鼠与非Tg组相比表达。实验期间未观察到TGF-β基因的过度表达，提示HSP 47基因可能与不可逆性肺纤维化的进展有关，但不是肺纤维化的触发因子。但在实验模型中，HSP 47基因与肺气肿的关系尚不明确。在进行性肺纤维化过程中，HSP 47基因的调控可调控胶原的沉积。

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.