The role of collagenases in experimental pulmonary fibrosis
The role of collagenases in experimental pulmonary fibrosis
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DOI：
10.1016/j.pupt.2007.10.006
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Nakanishi, Yoichi
中科院分区：
文献类型：
--
作者：
Ouchi, Hiroshi;Fujita, Masaki;Nakanishi, Yoichi
基质金属蛋白酶（MMPs）的表达在细胞外基质沉积中起着至关重要的作用。尽管目前已有一些证据表明明胶酶有助于肺纤维化的发展，但胶原酶的作用仍不确定。在这项研究中，我们试图用博莱霉素诱导的肺纤维化模型来确定胶原酶的作用。博莱霉素经气管内灌注小鼠。对支气管肺泡灌洗液（BAL）标本进行明胶和酪蛋白酶谱分析以及免疫印迹分析。肺组织学和羟脯氨酸含量也进行了评估。同时口服MMPs抑制剂CGS27023A。根据酶谱和免疫组织化学的数据，博来霉素给药后BAL液中诱导胶原酶。MMPs抑制剂CGS27023A与博来霉素合用可导致肺纤维化恶化，并抑制胶原酶。在博莱霉素诱导的肺纤维化发展的后期，CGS27023A主要诱导肺纤维化的恶化，而不是早期。目前的数据表明，胶原酶在博莱霉素诱导的肺纤维化模型中具有抗纤维化作用。在博莱霉素诱导的小鼠肺纤维化中，胶原酶对纤维化期的影响大于炎症期。(C) 2007 Elsevier Ltd.版权所有。
Matrix metalloproteinases (MMPs) expression plays a critical role in extracellular matrix deposition. Although several pieces of evidence have so far indicated that gelatinase contributes to the development of pulmonary fibrosis, the role of collagenase remains uncertain. In this study, we attempted to determine the role of collagenase using a bleomycin-induced pulmonary fibrosis model.Bleomycin was instilled into mice intratracheally. Bronchoalveolar lavage fluid (BAL) specimens were analyzed for gelatin and casein zymography, as well as by immunoblotting. The histology of the lungs and hydroxyproline contents were also assessed. MMPs inhibitor, CGS27023A, was simultaneously orally administered.Collagenases were induced in BAL fluids after bleomycin administration based on the data of zymography and immunohistochemistry. The co-administration of MMPs inhibitor, CGS27023A, with bleomycin resulted in worsening pulmonary fibrosis with inhibition of collagenase. The worsening of pulmonary fibrosis was mainly induced by CGS27023A administration in the late phase of bleomycin-induced pulmonary fibrosis development, but not in the early phase.The present data indicated that collagenase plays an anti-fibrotic role in the bleomycin-induced pulmonary fibrosis model. Collagenase has a greater effect on fibrosis phase than inflammatory phase in the bleomycin-induced pulmonary fibrosis in the mice. (C) 2007 Elsevier Ltd. All rights reserved.