@Article {Beaulieu2000752，作者= {Beaulieu，Delphine和Attwe，Aya and Breau，Marielle和Lipskaia，Larissa和Marcos，Elisabeth和Marcos，Elisabeth and Born，Emmanuelle和Huang，Huang，Jin and Jin and Abid and Abid，Shariq and Shariq and derumeaux and derumeaux and genevi {Houssaini，Amal和Maitre，Bernard和Lefevre，Marine和Vienney，Nora和Bertolino，Philippe和Jaber，Sara和Sara和Noureddine，Hiba和Goehrig，Delphine和Delphine和Delphine和Vindrieux，David and David and Bernard，David and Bernard，David and David and Adnot，Serga and Serge，title = phatospase A2受体1促进阻塞性肺部疾病中的肺细胞衰老和肺气肿，体积= {58}，数字= {2}，Elocation-id = {2000752}，年= {2021}，doi = {10.1183/13993003.003.003.00752-2020}，，发布者= {欧洲呼吸社会}188bet官网地址，摘要= {背景细胞衰老是与年龄相关功能障碍和疾病的关键过程，尤其是慢性阻塞性肺疾病（COPD）。我们先前以前鉴定出通过Janus激酶（JAK）/信号传感器和转录（STAT）信号传导活化剂作用磷脂酶A2受体1（PLA2R1）作为细胞衰老的阳性调节剂。然而，它在病理学中的作用仍然未知。在这里，我们评估了PLA2R1诱导的COPD和肺部肺气肿发病机制。方法我们评估了来自COPD患者的肺和培养的肺细胞和受PLA2R1敲低，PLA2R1基因转导和治疗JAK1/2抑制剂治疗的肺和培养的肺细胞的细胞衰老。为了评估PLA2R1上调是否引起了肺部病变，我们开发了过表达PLA2R1（PLA2R1-TG）（PLA2R1-TG）的转基因小鼠和带有PLA2R1基因的慢病毒载体（LV-PLA2R1小鼠）。在COPD肺中表现出衰老特征的各种细胞类型。PLA2R1敲低扩大了这些细胞的人口加倍能力，并抑制了其促炎性衰老相关的分泌表型（SASP）。 PLA2R1-mediated cell senescence in COPD was largely reversed by treatment with the potent JAK1/2 inhibitor ruxolitinib. Five-month-old PLA2R1-TG mice exhibited lung cell senescence, and developed lung emphysema and lung fibrosis together with pulmonary hypertension. Treatment with ruxolitinib induced reversal of lung emphysema and fibrosis. LV-PLA2R1-treated mice developed lung emphysema within 4 weeks and this was markedly attenuated by concomitant ruxolitinib treatment.Conclusions Our data support a major role for PLA2R1 activation in driving lung cell senescence and lung alterations in COPD. Targeting JAK1/2 may represent a promising therapeutic approach for COPD.PLA2R1 is a potent regulator of lung cell senescence in COPD, with JAK/STAT signalling as a major effector. Inhibition of JAK1/2 attenuates PLA2R1-induced lung alterations in murine models and so may represent a promising therapeutic approach for COPD. http://bit.ly/3i7yT3H}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/58/2/2000752}, eprint = {//www.qdcxjkg.com/content/58/2/2000752.full.pdf}, journal = {European Respiratory Journal} }