Cavin1; a regulator of lung function and macrophage phenotype.
Cavin1; a regulator of lung function and macrophage phenotype.
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DOI：
10.1371/journal.pone.0062045
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Summer R
中科院分区：
文献类型：
--
作者：
Govender P;Romero F;Shah D;Paez J;Ding SY;Liu L;Gower A;Baez E;Aly SS;Pilch P;Summer R
小窝是细胞膜内陷结构，在脂肪组织、内皮细胞和肺中高度丰富。小窝的形成依赖于多种结构蛋白的表达，这些结构蛋白作为这些膜内陷的支架。Cavin1是一种新发现的结构蛋白，其在小鼠中的缺失会导致小窝形成缺失以及脂肪营养不良表型的发展。在这项研究中，我们试图探究Cavin1在肺中的功能作用。Cavin1缺陷小鼠的远端肺形态发生显著改变，并表现出明显的生理变化，尤其是肺弹性增加。远端肺结构的变化与细胞过多以及肺巨噬细胞的积聚有关。肺巨噬细胞的增加没有伴随单核细胞循环数量的变化，也没有增殖增加的证据。然而，肺巨噬细胞的增加与Cavin1 - / -小鼠支气管肺泡灌洗液中巨噬细胞趋化因子CXCL2和CCL2水平升高有关，这提示了这些细胞积聚的一种可能机制。此外，与野生型小鼠的巨噬细胞相比，Cavin1 - / -小鼠的肺巨噬细胞更大，并且在基因表达上有可测量的差异。有趣的是，Cavin1 - / -小鼠的脂肪组织中巨噬细胞也增加，但在肝脏、肾脏或骨骼肌中没有增加，并且在Caveolin1 - / -小鼠的肺和脂肪组织中观察到了类似的巨噬细胞积聚的组织特异性。总之，这项研究证明了Cavin1在肺内稳态中的重要作用，并表明小窝结构蛋白对于调节肺中巨噬细胞的数量和表型是必要的。
Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung architecture were associated with hypercellularity and the accumulation of lung macrophages. The increases in lung macrophages occurred without changes to circulating numbers of mononuclear cells and without evidence for increased proliferation. However, the increases in lung macrophages were associated with higher levels of macrophage chemotactic factors CXCL2 and CCL2 in BAL fluid from Cavin1−/− mice suggesting a possible mechanism by which these cells accumulate. In addition, lung macrophages from Cavin1−/− mice were larger and displayed measurable differences in gene expression when compared to macrophages from wild-type mice. Interestingly, macrophages were also increased in adipose tissue but not in liver, kidney or skeletal muscle from Cavin1−/− mice, and similar tissue specificity for macrophage accumulation was observed in lungs and adipose tissue from Caveolin1−/− mice. In conclusion, this study demonstrates an important role for Cavin1 in lung homeostasis and suggests that caveolae structural proteins are necessary for regulating macrophage number and phenotype in the lung.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.8
作者：
Razani, B;Combs, TP;Lisanti, MP
通讯作者：
Lisanti, MP
影响因子：
56.9
作者：
Drab, M;Verkade, P;Kurzchalia, TV
通讯作者：
Kurzchalia, TV
影响因子：
29
作者：
Liu L;Brown D;McKee M;Lebrasseur NK;Yang D;Albrecht KH;Ravid K;Pilch PF
通讯作者：
Pilch PF
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP