The Rise and Fall of Hyaluronan in Respiratory Diseases.
The Rise and Fall of Hyaluronan in Respiratory Diseases.
复制标题
DOI：
10.1155/2015/712507
复制
发表时间：
2015
影响因子：
--
通讯作者：
Aronica MA
中科院分区：
文献类型：
--
作者：
Lauer ME;Dweik RA;Garantziotis S;Aronica MA
在正常气道中，透明质酸（HA）基质主要位于气道粘膜下层、肺血管壁内，并且在较小程度上位于肺泡内。肺损伤后，HA基质水平升高，在这些区域和呼吸道分泌物中积累，与损伤程度相关。动物模型已经提供了对HA在肺损伤和修复的发作中的作用的重要见解，通常表明HA合成的诱导是通常在纤维化之前的早期事件。在发炎气道中积累的HA具有高分子量（>1600 kDa），但可通过对HA病理生物学具有深远影响的炎症和疾病相关机制分解成较小片段（<150 kDa）。在气道炎症期间，HA通常通过酶肿瘤坏死因子刺激基因-6（TSG-6）用来自α-间抑制剂的重链共价修饰，并且这种修饰促进白细胞与HA基质在炎症部位的相互作用。HA的清除及其恢复到正常水平对于炎症的适当解决至关重要。这些数据将HA基质描绘为正常气道生理学的重要组成部分，并说明其在各种呼吸系统疾病中的组织损伤和修复过程中的不可或缺的作用。
In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.