Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma.
Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma.
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DOI：
10.1016/j.matbio.2010.12.003
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发表时间：
2011-03
期刊：
影响因子：
6.9
通讯作者：
Aronica, Mark A.
中科院分区：
文献类型：
--
作者：
Cheng, Georgiana;Swaidani, Shadi;Sharma, Manisha;Lauer, Mark E.;Hascall, Vincent C.;Aronica, Mark A.
哮喘是一种以气道重塑为特征的气道慢性炎症性疾病，其包括细胞外基质（ECM）的变化。然而，ECM在介导这些变化中的作用知之甚少。透明质酸（HA）是ECM的主要成分，与哮喘以及许多其他生物学过程有关。我们的研究探讨了HA的合成，沉积，定位和降解过程中的急性和慢性小鼠模型卵清蛋白（OVA）诱导的过敏性肺部炎症。在8周的攻击方案期间，使小鼠致敏，用OVA攻击并在不同时间点处死。收集支气管肺泡灌洗液（BAL）、血液和肺组织用于研究。RNA、HA、蛋白质和组织病理学分析。肺切片和BAL液的分析显示抗原暴露24小时内HA水平早期沉积和增加。在BAL中HA水平在第8天达到峰值，而炎性细胞恢复在第6天达到峰值。RNA水平上的透明质酸合成酶（HAS）1和HAS 2在抗原暴露2小时内达到峰值，而RNA水平上的透明质酸酶（HYAL）1和HYAL 2下降。炎症细胞浸润和胶原沉积与肺内的HA沉积共定位。这些数据支持HA在哮喘小鼠模型中炎症和气道重塑的发病机制中的作用。HA沉积主要是由于HAS 1和HAS 2的上调。此外，HA似乎为炎性细胞积累以及新的胶原蛋白合成和沉积提供了支架。
Asthma is a chronic inflammatory disease of the airways characterized by airway remodeling, which includes changes in the extracellular matrix (ECM). However the role of the ECM in mediating these changes is poorly understood. Hyaluronan (HA), a major component of the ECM, has been implicated in asthma as well as in many other biological processes. Our study investigates the processes involved in HA synthesis, deposition, localization and degradation during an acute and chronic murine model of ovalbumin (OVA)-induced allergic pulmonary inflammation. Mice were sensitized, challenged to OVA and sacrificed at various time points during an 8-week challenge protocol. Bronchoalveolar lavage (BAL) fluids, blood, and lung tissue were collected for study. RNA, HA, protein and histopathology were analyzed. Analyses of lung sections and BAL fluids revealed an early deposition and an increase in HA levels within 24 hours of antigen exposure. HA levels peaked at day 8 in BAL, while inflammatory cell recovery peaked at day 6. Hyaluronan synthase (HAS)1 and HAS2 on RNA levels peaked within 2 hours of antigen exposure, while hyaluronidase (HYAL)1 and HYAL2 on RNA levels decreased. Both inflammatory cell infiltrates and collagen deposition co-localized with HA deposition within the lungs. These data support a role for HA in the pathogenesis of inflammation and airway remodeling in a murine model of asthma. HA deposition appears largely due to up regulation of HAS1 and HAS2. In addition, HA appears to provide the scaffolding for inflammatory cell accumulation as well as for new collagen synthesis and deposition.
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影响因子：
20.3
作者：
Milinkovic, M;Antin, JH;Sackstein, R
通讯作者：
Sackstein, R
DOI：
10.1164/ajrccm.160.2.9809040
发表时间：
1999-08-01
影响因子：
24.7
作者：
Huang, J;Olivenstein, R;Ludwig, M
通讯作者：
Ludwig, M
DOI：
10.1046/j.1440-1681.2001.03426.x
发表时间：
2001-03-01
影响因子：
2.9
作者：
Johnson, PRA
通讯作者：
Johnson, PRA
DOI：
10.1165/ajrcmb.23.4.3875
发表时间：
2000-10-01
影响因子：
6.4
作者：
Ohkawara, Y;Tamura, G;Shirato, K
通讯作者：
Shirato, K
影响因子：
4.8
作者：
Lauer, Mark E.;Fulop, Csaba;Hascall, Vincent C.
通讯作者：
Hascall, Vincent C.