Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics.
Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics.
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DOI：
10.1002/lary.20173
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发表时间：
2009-07
期刊：
影响因子：
2.6
通讯作者：
Hebda, Patricia A.
中科院分区：
文献类型：
--
作者：
Sandulache, Vlad C.;Singh, Tripti;Li-Korotky, Ha Sheng;Lo, Chia Y.;Otteson, Todd D.;Barsic, Mark;Dohar, Joseph E.;Hebda, Patricia A.
研究气道黏膜修复过程中环氧合酶（考克斯）-2/前列腺素（PG）E2信号通路的激活及其在创伤愈合过程中的作用。前瞻性动物研究。通过环甲膜切开术进入声门下。关闭假气道，对受伤气道进行激光损伤并关闭。分别于伤后12小时、24小时、48小时和72小时收集声门下组织。在术前和处死时收集分泌物。用定量逆转录聚合酶链反应分析炎症基因表达。在存在或不存在考克斯抑制剂的情况下，将声门下/气管外植体暴露于外源性IL-1β。使用酶联免疫测定法测定前列腺素E2水平。在存在或不存在前列腺素E2的情况下测定人气道成纤维细胞迁移和胶原收缩。激光损伤触发粘膜IL-1β和考克斯-2基因表达的快速、剂量依赖性增加，其解剖学分布与距损伤部位的距离成比例。基因上调与PGE 2粘膜分泌水平的剂量依赖性增加相关。离体分析表明IL-1β负责考克斯-2/PGE 2通路的激活。前列腺素E2以特定的剂量依赖性方式差异性地抑制气道成纤维细胞迁移和收缩。PGE 2在粘膜炎症期间被激活，并起到减少粘膜伤口床中纤维增生活性的作用。在声门下狭窄（SGS）的发展过程中，响应于损伤产生的PGE 2水平可能不足以钝化SGS成纤维细胞的内在纤维形成表型，导致过度瘢痕形成。
To characterize the activation of cyclooxygenase (COX)-2/prostaglandin (PG) E2 signaling during airway mucosal repair and its subsequent role during the wound healing process. Prospective animal study. The subglottis was approached via cricothyroidotomy. Sham airways were closed, and wounded airways were subjected to laser injury and closed. Subglottic tissue was harvested at 12 hours, 24 hours, 48 hours, and 72 hours postinjury. Secretions were collected preoperatively and at time of sacrifice. Inflammatory gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction. Subglottic/tracheal explants were exposed to exogenous IL-1β in the presence or absence of COX inhibitors. Explant-produced PGE2 levels were assayed using enzyme linked immunoassays. Human airway fibroblast migration and collagen contraction were assayed in the presence or absence of prostaglandin E2. Laser injury triggers a rapid, dose-dependent increase in mucosal IL-1β and COX-2 gene expression, with an anatomical distribution proportional to the distance from the site of injury. Gene up-regulation correlates with dose-dependent increases in PGE2 mucosal secretion levels. Ex vivo analysis indicates IL-1β is responsible for the activation of the COX-2/PGE2 pathway. Prostaglandin E2 differentially inhibits airway fibroblast migration and contraction in a specific, dose-dependent manner. PGE2 is activated during mucosal inflammation and acts to decrease fibroplastic activity in the mucosal wound bed. During subglottic stenosis (SGS) development, the levels of PGE2 generated in response to injury may be insufficient to blunt the intrinsically fibroplastic phenotype of SGS fibroblasts, resulting in excessive scarring.
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