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Immune checkpoint protein VSIG4 as a biomarker of aging in murine adipose tissue.
Aging Cell ( IF 7.8 ) Pub Date : 2020-08-28 , DOI: 10.1111/acel.13219
Brandon M Hall 1 , Anatoli S Gleiberman 1 , Evguenia Strom 1 , Peter A Krasnov 1 , David Frescas 1 , Slavoljub Vujcic 1 , Olga V Leontieva 2 , Marina P Antoch 2 , Valeria Kogan 3 , Igor E Koman 3 , Yi Zhu 4 , Tamara Tchkonia 4 , James L Kirkland 4 , Olga B Chernova 1 , Andrei V Gudkov 1, 5, 6
Affiliation  

Adipose tissue is recognized as a major source of systemic inflammation with age, driving age‐related tissue dysfunction and pathogenesis. Macrophages (Mφ) are central to these changes yet adipose tissue Mφ (ATMs) from aged mice remain poorly characterized. To identify biomarkers underlying changes in aged adipose tissue, we performed an unbiased RNA‐seq analysis of ATMs from young (8‐week‐old) and healthy aged (80‐week‐old) mice. One of the genes identified, V‐set immunoglobulin‐domain‐containing 4 (VSIG4/CRIg), encodes a Mφ‐associated complement receptor and B7 family‐related immune checkpoint protein. Here, we demonstrate that Vsig4 expression is highly upregulated with age in perigonadal white adipose tissue (gWAT) in two mouse strains (inbred C57BL/6J and outbred NIH Swiss) independent of gender. The accumulation of VSIG4 was mainly attributed to a fourfold increase in the proportion of VSIG4+ ATMs (13%–52%). In a longitudinal study, VSIG4 expression in gWAT showed a strong correlation with age within a cohort of male and female mice and correlated strongly with physiological frailty index (PFI, a multi‐parameter assessment of health) in male mice. Our results indicate that VSIG4 is a novel biomarker of aged murine ATMs. VSIG4 expression was also found to be elevated in other aging tissues (e.g., thymus) and was strongly induced in tumor‐adjacent stroma in cases of spontaneous and xenograft lung cancer models. VSIG4 expression was recently associated with cancer and several inflammatory diseases with diagnostic and prognostic potential in both mice and humans. Further investigation is required to determine whether VSIG4‐positive Mφ contribute to immunosenescence and/or systemic age‐related deficits.

中文翻译:

免疫检查点蛋白 VSIG4 作为鼠脂肪组织衰老的生物标志物。

随着年龄的增长,脂肪组织被认为是全身炎症的主要来源,导致与年龄相关的组织功能障碍和发病机制。巨噬细胞 (Mφ) 是这些变化的核心,但来自老年小鼠的脂肪组织 Mφ (ATM) 的特征仍然很差。为了确定老年脂肪组织潜在变化的生物标志物,我们对来自年轻(8 周龄)和健康老年(80 周龄)小鼠的 ATM 进行了无偏的 RNA-seq 分析。鉴定出的基因之一,V-set 免疫球蛋白域包含 4 (VSIG4/CRIg),编码 Mφ 相关补体受体和 B7 家族相关免疫检查点蛋白。在这里,我们证明Vsig4在与性别无关的两种小鼠品系(近交 C57BL/6J 和远交 NIH Swiss)中,随着年龄的增长,表达在性腺周围白色脂肪组织 (gWAT) 中高度上调。VSIG4 的积累主要归因于 VSIG4 +的比例增加了四倍自动取款机(13%–52%)。在一项纵向研究中,gWAT 中的 VSIG4 表达与雄性和雌性小鼠队列中的年龄密切相关,并与雄性小鼠的生理衰弱指数(PFI,健康的多参数评估)密切相关。我们的结果表明 VSIG4 是老年鼠类 ATM 的新型生物标志物。还发现 VSIG4 表达在其他衰老组织(例如胸腺)中升高,并且在自发性和异种移植肺癌模型的肿瘤相邻基质中被强烈诱导。VSIG4 表达最近与癌症和几种在小鼠和人类中具有诊断和预后潜力的炎症性疾病有关。需要进一步研究以确定 VSIG4 阳性 Mφ 是否会导致免疫衰老和/或全身性年龄相关缺陷。
更新日期:2020-10-23
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