Investigation of role for MafB in the pathogenesis of chronic obstructive pulmonary disease using MafB gene targeted mice

采用巨噬细胞清道夫受体启动子显性阴性MafB转基因（MSR-DN-MafBTG）小鼠，研究MafB在慢性阻塞性肺疾病（COPD）发病中的作用。与野生型小鼠（WT）相比，TG小鼠体内注射弹性蛋白酶后的平均线性截距显著降低。在TG小鼠中，具有投射伪足的肺泡巨噬细胞（AM）的数量显著减少。此外，在DN-MafB Tg小鼠的BAL细胞中，F4/80中等阳性和CD 11b弱或中等阳性AM的数量减少，这些AM是成熟AM的相当大的细胞亚群。此外，MMP-9和-12在DN-MafB Tg小鼠的BAL细胞中的表达被显著抑制。由于MMPs可加重肺气肿，MafB可能通过改变巨噬细胞的成熟和MMPs的表达而参与肺气肿的发病。

Role of MafB in the pathogenesis of chronic obstructive pulmonary disease (COPD) was investigated using macrophage scavenger receptor promoter dominant negative-MafB transgenic (MSR-DN-MafB TG) mice. Mean linear intercept after intratracheal administration of elastase was significantly reduced in TG mice compared to the wild type mice (WT). In TG mice, number of alveolar macrophages (AMs) with projected pseudopods was significantly reduced. In addition, number of F4/80 intermediately positive and CD11b weakly or intermediately positive AMs, considerable cell subsets of matured AMs, decreased in BAL cells of DN-MafB Tg mice. Furthermore, the expression of MMP-9 and -12 was suppressed significantly in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema pathogenesis through altering the maturation of macrophages and the expression of MMPs.