β-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY(2017)
摘要
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.
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关键词
beta(2)-microglobulin,epithelial cells,senescence,CSE,emphysema
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