Reversal of emphysema by restoration of pulmonary endothelial cells.
Reversal of emphysema by restoration of pulmonary endothelial cells.
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通过肺内皮细胞的恢复来恢复肺气肿。
DOI：
10.1084/jem.20200938
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发表时间：
2021-08-02
期刊：
影响因子：
--
通讯作者：
Choi AMK
中科院分区：
文献类型：
--
作者：
Hisata S;Racanelli AC;Kermani P;Schreiner R;Houghton S;Palikuqi B;Kunar B;Zhou A;McConn K;Capili A;Redmond D;Nolan DJ;Ginsberg M;Ding BS;Martinez FJ;Scandura JM;Cloonan SM;Rafii S;Choi AMK
我们测试了内皮功能障碍在COPD/肺气肿发生发展中的作用。我们发现肺内皮细胞的修复和内皮源性富含亮氨酸的α-2糖蛋白的阻断扰乱了慢性阻塞性肺疾病/肺气肿的发病机制。慢性阻塞性肺疾病(COPD)的特点是呼吸道炎症和空域扩大(肺气肿)，导致气流阻塞和最终呼吸衰竭。微血管功能障碍与COPD/肺气肿相关。然而，目前尚不清楚内皮异常是否推动了COPD/肺气肿的病理和/或纠正内皮功能障碍是否具有治疗潜力。在这里，我们展示了内皮细胞在人类组织中COPD/肺气肿发病机制中的中心地位，并使用了弹性酶诱导的小鼠肺气肿模型。空域疾病表现为显著的内皮细胞丢失，转录图谱提示细胞凋亡、血管生成和炎症状态。这种肺泡破坏是通过静脉注射健康的肺内皮细胞来挽救的。富含亮氨酸的α-2-糖蛋白-1(LRG1)是肺气肿的诱因，从内皮细胞中缺失LRG1可以挽救血管疏松和肺泡退缩。因此，通过再生方法靶向内皮细胞生物学和/或抑制LRG1通路可能是治疗COPD/肺气肿的巨大潜力的策略。
We tested the role of endothelial dysfunction in the development of COPD/emphysema. We found that restoration of lung endothelial cells and blockade of endothelial-derived leucine-rich α-2-glycoprotein perturbs the pathogenesis of COPD/emphysema. Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema. Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state. This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells. Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression. Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema.
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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
2.6
作者：
Kropski JA;Richmond BW;Gaskill CF;Foronjy RF;Majka SM
通讯作者：
Majka SM
影响因子：
13.6
作者：
Hong, Quan;Zhang, Lu;Lee, Kyung
通讯作者：
Lee, Kyung
影响因子：
4
作者：
Andersen JD;Boylan KL;Jemmerson R;Geller MA;Misemer B;Harrington KM;Weivoda S;Witthuhn BA;Argenta P;Vogel RI;Skubitz AP
通讯作者：
Skubitz AP
影响因子：
15.9
作者：
Kasahara, Y;Tuder, RM;Voelkel, NF
通讯作者：
Voelkel, NF