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,Nora AU - Bertolino, Philippe AU - Jaber, Sara AU - Noureddine, Hiba AU - Goehrig, Delphine AU - Vindrieux, David AU - Bernard, David AU - Adnot, Serge Y1 - 201/08/01 UR - //www.qdcxjkg.com/content/58/2/2000752.abstract N2 -背景细胞衰老是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病(COPD)。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的正向调节因子。然而，它在病理学中的作用仍然未知。在这里，我们评估了pla2r1在COPD和肺气肿发病机制中诱导的衰老。我们评估了COPD患者和对照组肺细胞的细胞衰老情况，这些患者分别接受PLA2R1敲低、PLA2R1基因转导和JAK1/2抑制剂ruxolitinib治疗。为了评估PLA2R1上调是否会导致肺部病变，我们开发了过表达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(LV-PLA2R1小鼠)。结果我们发现PLA2R1在COPD肺中多种具有衰老特征的细胞类型中过表达。PLA2R1的敲除延长了这些细胞的种群倍增能力，并抑制了它们促炎衰老相关的分泌表型(SASP)。COPD中pla2r1介导的细胞衰老通过强效JAK1/2抑制剂ruxolitinib治疗在很大程度上得到逆转。5月龄PLA2R1-TG小鼠出现肺细胞衰老，并发肺气肿、肺纤维化及肺动脉高压。 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 -