Altered MCM protein levels and autophagic flux in aged and systemic sclerosis dermal fibroblasts.
Altered MCM protein levels and autophagic flux in aged and systemic sclerosis dermal fibroblasts.
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DOI：
10.1038/jid.2014.69
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发表时间：
2014-09
影响因子：
6.5
通讯作者：
Dengjel, Joern
中科院分区：
文献类型：
--
作者：
Dumit, Veronica I.;Kuettner, Victoria;Kaeppler, Jakob;Piera-Velazquez, Sonsoles;Jimenez, Sergio A.;Bruckner-Tuderman, Leena;Uitto, Jouni;Dengjel, Joern
衰老是许多疾病的共同危险因素。随着年龄的增长，不溶性细胞外基质的水平增加，导致许多组织的硬度增加。在纤维化疾病如系统性硬化症（SSc）中也可以观察到基质积累。虽然皮肤内在的老化过程在表型上与SSc不同，但在这里，我们证明了培养中老化和SSc皮肤成纤维细胞的相似行为。我们使用定量蛋白质组学来表征来自不同年龄的健康受试者和来自SSc患者的真皮成纤维细胞的表型。我们的研究结果表明，参与DNA和RNA加工的蛋白质随着年龄和SSc的增加而减少，而参与线粒体和其他代谢过程的蛋白质则相反。具体而言，迷你染色体维护（MCM）解旋酶蛋白是不丰富的年龄和SSc，他们表现出改变亚细胞分布。我们观察到较低水平的MCM7与衰老和SSc细胞的细胞增殖降低、自噬能力降低和细胞内蛋白表达表型升高相关。此外，我们发现SSc成纤维细胞比健康的成纤维细胞表现出更高的衰老水平，这表明纤维化疾病和衰老过程之间存在进一步的相似性。因此，在分子水平上，SSc成纤维细胞表现出来自老化皮肤的成纤维细胞的内在特征。
Aging is a common risk factor of many disorders. With age, the level of insoluble extracellular matrix increases leading to increased stiffness of a number of tissues. Matrix accumulation can also be observed in fibrotic disorders, such as systemic sclerosis (SSc). Although the intrinsic aging process in skin is phenotypically distinct from SSc, here we demonstrate similar behavior of aged and SSc skin fibroblasts in culture. We have used quantitative proteomics to characterize the phenotype of dermal fibroblasts from healthy subjects of various ages and from patients with SSc. Our results demonstrate that proteins involved in DNA and RNA processing decrease with age and in SSc, while those involved in mitochondrial and other metabolic processes behave the opposite. Specifically, mini-chromosome maintenance (MCM) helicase proteins are less abundant with age and SSc, and they exhibit an altered subcellular distribution. We observed that lower levels of MCM7 correlate with reduced cell proliferation, lower autophagic capacity and higher intracellular protein expression phenotypes of aged and SSc cells. Additionally, we show that SSc fibroblasts exhibit higher levels of senescence than their healthy counterparts, suggesting further similarities between the fibrotic disorder and the aging process. Hence, at the molecular level, SSc fibroblasts exhibit intrinsic characteristics of fibroblasts from aged skin.
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影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
--
作者：
Akimov, Vyacheslav;Rigbolt, Kristoffer T. G.;Blagoev, Blagoy
通讯作者：
Blagoev, Blagoy
DOI：
10.1196/annals.1333.061
发表时间：
2005-01-01
期刊：
MAILLARD REACTION: CHEMISTRY AT THE INTERFACE OF NUTRITION, AGING, AND DISEASE
影响因子：
--
作者：
Monnier, VM;Mustata, GT;Sell, DR
通讯作者：
Sell, DR
影响因子：
4.8
作者：
Hubbi, Maimon E.;Hu, Hongxia;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.
影响因子：
16
作者：
Hubbi ME;Luo W;Baek JH;Semenza GL
通讯作者：
Semenza GL