戴尔芬% % 0期刊文章% Beaulieu Attwe,阿雅% Breau, Marielle % Lipskaia,拉里萨%马科斯,伊丽莎白%出生,Emmanuelle %黄,金%阿比德,部门% Derumeaux,吉纳维芙% Houssaini,阿玛尔%管家,伯纳德%勒费弗,海洋% Vienney,诺拉% Bertolino,菲利普%贾比尔,莎拉%误,Hiba % Goehrig,戴尔芬% Vindrieux,大卫%伯纳德,大卫% Adnot,哔叽% T磷脂酶A2受体1促进肺癌细胞衰老和肺气肿,阻塞性肺疾病2021% % D J R 10.1183/13993003.00752 -2020%欧洲呼吸杂志% P 2000752 % V 58% N 2% X背景,细胞衰老是一个关键的过程与年龄有关的功能障碍和疾病,特别是慢性阻塞性肺病(COPD)。我们之前确定磷脂酶A2受体1 (PLA2R1)作为细胞衰老作用的积极的监管机构通过Janus激酶(激酶)/信号传感器和转录激活(STAT)信号。其在病理作用,然而,仍然未知。在这里,我们评估PLA2R1-induced衰老在慢性阻塞性肺病和肺肺气肿发病机制。方法我们评估细胞衰老在COPD患者肺和肺细胞培养和控制受到PLA2R1击倒,PLA2R1 JAK1/2抑制剂ruxolitinib基因转导和治疗。评估是否PLA2R1 upregulation肺部病变引起的,我们开发了转基因小鼠overexpressing PLA2R1 (PLA2R1-TG)和气管内的野生型小鼠注射慢病毒载体携带PLA2R1基因(LV-PLA2R1老鼠)。结果我们发现PLA2R1过表达在不同的细胞类型表现出衰老特征在COPD肺。PLA2R1击倒延长人口翻了一番这些细胞的能力,抑制促炎senescence-associated分泌表型(SASP)。PLA2R1-mediated在COPD主要是逆转细胞衰老与强有力的JAK1/2抑制剂ruxolitinib治疗。五个月PLA2R1-TG老鼠表现出肺细胞衰老,产生肺肺气肿和肺纤维化与肺动脉高压。治疗ruxolitinib诱导肺肺气肿和纤维化的逆转。 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 %U //www.qdcxjkg.com/content/erj/58/2/2000752.full.pdf