Correlation Profile of Suppression of Tumorigenicity 2 and/or Interleukin-33 with Biomarkers in the Adipose Tissue of Individuals with Different Metabolic States.
Correlation Profile of Suppression of Tumorigenicity 2 and/or Interleukin-33 with Biomarkers in the Adipose Tissue of Individuals with Different Metabolic States.
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DOI：
10.2147/dmso.s251978
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ahmad R
中科院分区：
文献类型：
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作者：
Hasan A;Kochumon S;Al-Ozairi E;Tuomilehto J;Al-Mulla F;Ahmad R
致瘤性抑制2（ST 2）有两种主要剪接变体，包括膜结合（ST 2）形式和分泌可溶形式（sST 2），前者激活髓样分化初级反应88（MyD 88）/核因子-κ B（NF-κB）信号通路，后者充当ST 2配体白细胞介素（IL）-33的诱饵受体。IL-33/ST 2轴对肥胖、胰岛素抵抗和2型糖尿病（T2 D）具有保护作用。在人类中，脂肪组织IL-33与糖化血红蛋白、ST 2和其他免疫代谢介质显示出不同的相关性，这取决于个体的血糖健康状况。我们确定脂肪组织ST 2是否与免疫代谢介质表现出不同的相关性，以及ST 2和/或IL-33是否与细胞内信号分子相关。共纳入91名正常糖尿病、前驱糖尿病和T2 D成人。在测量其人体测量和生化参数后，分离皮下脂肪组织并测量生物标志物的mRNA表达。在正常脂肪组织中，脂肪组织ST 2与趋化因子（C-C基序）配体（CCL）-2，CCL 5，IL-12，纤维蛋白原样蛋白2（FGL 2）和干扰素调节因子（IRF）-4直接相关，但与细胞色素C氧化酶亚基7A 1负相关。IL-33和ST 2与肿瘤坏死因子受体相关因子6（TRAF 6）、NF-κB和活化T细胞核因子5（NFAT 5）直接相关。在糖尿病前期个体中，ST 2与IL-5呈负相关，而IL-33与MyD 88和NF-κB呈正相关，而ST 2与之无关。在T2 D患者中，ST 2与CCL 2、IL-1β和IRF 5直接相关。IL-33和ST 2与MyD 88、TRAF 6和NF-κB直接相关。脂肪组织ST 2和IL-33与各种免疫代谢生物标志物显示出不同的相关性，这取决于个体的代谢状态。因此，靶向IL-33/ST 2轴可能成为对抗代谢紊乱的新疗法的基础。
The suppression of tumorigenicity 2 (ST2) has two main splice variants including a membrane bound (ST2) form, which activates the myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway, and a secreted soluble form (sST2), which acts as a decoy receptor for ST2 ligand, interleukin (IL)-33. The IL-33/ST2 axis is protective against obesity, insulin resistance, and type 2 diabetes (T2D). In humans, adipose tissue IL-33 displays distinct correlation profiles with glycated hemoglobin, ST2, and other immunometabolic mediators, depending on the glycemic health of the individuals. We determined whether adipose tissue ST2 displays distinct correlation profiles with immunometabolic mediators and whether ST2 and/or IL-33 are correlated with intracellular signaling molecules. A total of 91 adults with normal glycemia, prediabetes, and T2D were included. After measuring their anthropometric and biochemical parameters, subcutaneous adipose tissues were isolated and mRNA expression of biomarkers was measured. In individuals with normal glycemia, adipose tissue ST2 was directly correlated with chemokine (C-C motif) ligand (CCL)-2, CCL5, IL-12, fibrinogen-like protein 2 (FGL2) and interferon regulatory factor (IRF)-4, but inversely correlated with cytochrome C oxidase subunit 7A1. IL-33 and ST2 were directly correlated with tumor necrosis factor receptor-associated factor 6 (TRAF6), NF-κB, and nuclear factor of activated T-cells 5 (NFAT5). In individuals with prediabetes, ST2 was inversely correlated with IL-5, whereas IL-33 but not ST2 was directly correlated with MyD88 and NF-κB. In individuals with T2D, ST2 was directly correlated with CCL2, IL-1β, and IRF5. IL-33 and ST2 were directly correlated with MyD88, TRAF6, and NF-κB. Adipose tissue ST2 and IL-33 show different correlation profiles with various immunometabolic biomarkers depending on the metabolic state of the individuals. Therefore, targeting the IL-33/ST2 axis might form the basis for novel therapies to combat metabolic disorders.