TY -的T1 -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JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00752 -2020欧元六世- 58 - 2 SP - 2000752 AU比尤利戴尔芬盟——Attwe阿雅盟——Breau Marielle AU - Lipskaia,拉里萨盟-马科斯,伊丽莎白盟——出生,Emmanuelle盟——黄、金盟-阿比德,部门非盟- Derumeaux,吉纳维芙盟——Houssaini Amal盟——管家,伯纳德AU -勒费弗,海洋非盟- Vienney诺拉盟——Bertolino菲利普盟——贾比尔,莎拉盟,误Hiba盟——Goehrig戴尔芬盟——Vindrieux大卫AU -伯纳德,大卫盟——Adnot细胞衰老是与年龄相关的功能障碍和疾病，尤其是慢性阻塞性肺疾病(COPD)的关键过程。我们之前发现磷脂酶A2受体1 (PLA2R1)是通过Janus激酶(JAK)/信号传感器和转录激活剂(STAT)信号作用的细胞衰老正调节因子。然而，它在病理学中的作用仍然未知。在这里，我们评估了pla2r1诱导的衰老在COPD和肺气肿发病机制中的作用。研究人员检测了在PLA2R1基因下调、PLA2R1基因转导和JAK1/2抑制剂ruxolitinib治疗下COPD患者和对照组的肺细胞和培养的肺细胞的衰老情况。为了评估PLA2R1上调是否导致肺损伤，我们培养了过表达PLA2R1的转基因小鼠(PLA2R1- tg)，并气管内注射携带PLA2R1基因的慢病毒载体的野生型小鼠(LV-PLA2R1小鼠)。结果我们发现pl2r1在COPD肺中表现出衰老特征的各种细胞类型中过表达。PLA2R1的敲除延长了这些细胞的种群倍增能力，并抑制了它们的促炎衰老相关分泌表型(SASP)。有效的JAK1/2抑制剂ruxolitinib治疗后，COPD中pla2r1介导的细胞衰老在很大程度上得到逆转。 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 ER -