β2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence
β2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence
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β(2)-微球蛋白通过诱导肺上皮细胞衰老参与肺气肿的发生
DOI：
10.1152/ajplung.00516.2016
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发表时间：
2017-05-01
影响因子：
4.9
通讯作者：
Huang, Kewu
中科院分区：
文献类型：
--
作者：
Gao, Na;Wang, Ying;Huang, Kewu
β(2)-微球蛋白 (β M-2) 是主要组织相容性复合体 I 类 (MHC I) 的轻链，已被确定为促衰老因子，并通过驱动认知和再生障碍参与神经退行性疾病的发病机制。然而，很少有人关注 β M-2 在肺气肿发展中的作用。在这里，我们发现肺气肿患者血浆中 β M-2 的浓度显着高于正常对照受试者（1.89 +/- 0.12 vs. 1.42 +/- 0.06 mg/l，P < 0.01）。此外，肺气肿肺组织中β M-2的表达显着升高（39.90±1.97 vs. 23.94±2.11%，P < 0.01）。免疫荧光显示β M-2主要表达于前表面活性剂蛋白C阳性(pro-SPC+)肺泡上皮细胞和CD14(+)巨噬细胞。体外暴露于重组人 β M-2 和香烟烟雾提取物 (CSE) 会增强细胞衰老并抑制 A549 细胞的增殖，而抗 β M-2 抗体的存在可部分逆转这种情况。然而，抗 β M-2 抗体并不能减弱暴露于 CSE 的 A549 细胞中 IL-1 β、IL-6 和 TNF-α 的升高。免疫荧光显示在 A549 细胞上观察到 β M-2 和血色素沉着病基因 (HFE) 蛋白的共定位。这些数据表明βM-2可能通过诱导肺上皮细胞衰老和抑制参与肺气肿的发展。
beta(2)-Microglobulin (beta M-2), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of beta M-2 in the development of lung emphysema. Here, we found that concentrations of beta M-2 in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 +/- 0.12 vs. 1.42 +/- 0.06 mg/l, P < 0.01). Moreover, the expression of beta M-2 was significantly higher in lung tissue of emphysema (39.90 +/- 1.97 vs. 23.94 +/- 2.11%, P < 0.01). Immunofluorescence showed that beta M-2 was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14(+) macrophages. Exposure to recombinant human beta M-2 and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-beta M-2 antibody. However, anti-beta M-2 antibody did not attenuate the elevated production of IL-1 beta, IL-6, and TNF-alpha in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of beta M-2, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest beta M-2 might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.