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高循环水平的 S100A8/A9 复合物(钙卫蛋白)在日本男性腹部肥胖者中,以及肥胖小鼠脂肪组织中 S100A8 和 S100A9 表达失调。

High circulating levels of S100A8/A9 complex (calprotectin) in male Japanese with abdominal adiposity and dysregulated expression of S100A8 and S100A9 in adipose tissues of obese mice.

机构信息

Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.

出版信息

Biochem Biophys Res Commun. 2012 Mar 23;419(4):782-9. doi: 10.1016/j.bbrc.2012.02.102. Epub 2012 Feb 27.

Abstract

S100A8/A9 complex, calprotectin, which serves as an endogenous ligand for immune pathways, is associated with atherosclerosis. These proteins are reported to have several functions such as activating NADPH oxidase, binding toll-like receptor 4 and associated with the receptor for advanced glycation end-products. We recently reported S100A8 mRNA was highly expressed in mouse white adipose tissues and differentiated 3T3-L1 adipocytes. However, regulation of S100A9 expression in murine adipose tissue remains to be elucidated. The results of our studies in male Japanese, obese and control mice and cultured cells showed: (1) serum levels of S100A8/A9 complex, calprotectin, correlated with visceral fat area, body mass index, subcutaneous fat area, and leukocyte count in 500 Japanese men, and (2) higher mRNA expression levels of S100A8 in mature adipocyte fraction and S100A9 in stromal vascular cell fraction of obese mice, compared with those of lean mice. Overexpression of S100A8 and S100A9 in obese adipose tissue may be involved, at least partly, in not only high circulating levels of S100A8/A9 complex in abdominal obesity but also adipose and systemic tissue inflammation.

摘要

S100A8/A9 复合物、钙卫蛋白作为免疫途径的内源性配体,与动脉粥样硬化有关。这些蛋白被报道具有多种功能,如激活 NADPH 氧化酶、结合 toll 样受体 4 并与晚期糖基化终产物受体相关。我们最近报道 S100A8 mRNA 在小鼠白色脂肪组织和分化的 3T3-L1 脂肪细胞中高度表达。然而,鼠脂肪组织中 S100A9 表达的调节仍有待阐明。我们在雄性日本肥胖和对照小鼠以及培养细胞中的研究结果表明:(1)500 名日本男性中,S100A8/A9 复合物、钙卫蛋白的血清水平与内脏脂肪面积、体重指数、皮下脂肪面积和白细胞计数相关;(2)与瘦鼠相比,肥胖鼠成熟脂肪细胞部分 S100A8 表达水平升高,基质血管细胞部分 S100A9 表达水平升高。肥胖脂肪组织中 S100A8 和 S100A9 的过表达可能至少部分参与了不仅腹部肥胖患者循环 S100A8/A9 复合物水平升高,还参与了脂肪和全身组织炎症。

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