Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors.
Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors.
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DOI：
10.1111/acel.12040
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发表时间：
2013-04
期刊：
影响因子：
7.8
通讯作者：
Saito H
中科院分区：
文献类型：
--
作者：
Starr ME;Hu Y;Stromberg AJ;Carmical JR;Wood TG;Evers BM;Saito H
对由炎症性疾病引起的生理应激的耐受性随着年龄的增长而显著降低。高死亡率，增加细胞因子的产生和明显的血栓形成的特征性并发症的老年小鼠与急性全身炎症诱导注射脂多糖（LPS）。由于脂肪组织现在被认为是细胞因子的重要来源，我们确定了在雄性C57 BL/6小鼠中，在LPS诱导的炎症期间，衰老对内脏白色脂肪组织基因表达的影响。微阵列分析显示，LPS显著改变了6，025个基因的表达;其中，667个基因的表达显示出与年龄相关的差异。在许多属于炎症反应和凝血途径的基因中发现了与年龄相关的差异。几种促凝血因子的基因被LPS上调;其中，组织因子、血小板反应蛋白-1和纤溶酶原激活物抑制剂-1和-2表现出与年龄相关的表达增加，这可能有助于血栓形成。通过qRT-PCR、组织学检查和细胞组分分离进行的进一步分析表明，大多数炎症和凝血剂相关基因表达变化发生在常驻基质细胞中，而不是脂肪细胞或浸润细胞中。此外，303个基因的基础表达水平因衰老而改变，包括Sp 100-rs（Csprs）组分的表达增加。这项研究表明，脂肪组织是表达多种炎症和凝血因子基因的主要器官，并且其中许多因子的表达在急性炎症期间因衰老而显著改变。本文提供的数据为未来的研究提供了一个框架，旨在阐明脂肪组织对脓毒症和全身炎症期间年龄相关并发症的影响。
Tolerance to physiological stress resulting from inflammatory disease decreases significantly with age. High mortality rates, increased cytokine production and pronounced thrombosis are characteristic complications of aged mice with acute systemic inflammation induced by injection with lipopolysaccharide (LPS). As adipose tissue is now recognized as an important source of cytokines, we determined the effects of aging on visceral white adipose tissue gene expression during LPS-induced inflammation in male C57BL/6 mice. Microarray analysis revealed that the expression of 6,025 genes was significantly changed by LPS; of those, the expression of 667 showed an age-associated difference. Age-associated differences were found in many genes belonging to the inflammatory response and blood clotting pathways. Genes for several pro-coagulant factors were upregulated by LPS; among these, tissue factor, thrombospondin-1, and plasminogen activator inhibitors-1 and -2, exhibited age-associated increases in expression which could potentially contribute to augmented thrombosis. Further analysis by qRT-PCR, histological examination, and cell fraction separation revealed that most inflammatory and coagulant-related gene expression changes occur in resident stromal cells rather than adipocytes or infiltrating cells. Additionally, basal expression levels of 303 genes were altered by aging, including increased expression of component of Sp 100-rs (Csprs). This study indicates that adipose tissue is a major organ expressing genes for multiple inflammatory and coagulant factors and that the expression of many of these is significantly altered by aging during acute inflammation. Data presented here provides a framework for future studies aimed at elucidating the impact of adipose tissue on age-associated complications during sepsis and systemic inflammation.
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7.8
作者：
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通讯作者：
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