The source of circulating selenoprotein S and its association with type 2 diabetes mellitus and atherosclerosis: a preliminary study.
The source of circulating selenoprotein S and its association with type 2 diabetes mellitus and atherosclerosis: a preliminary study.
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循环硒蛋白S的来源及其与2型糖尿病和动脉粥样硬化的关系：初步研究
DOI：
10.1186/s12933-016-0388-3
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发表时间：
2016-04-28
影响因子：
9.3
通讯作者：
Du JL
中科院分区：
文献类型：
--
作者：
Yu SS;Men LL;Wu JL;Huang LW;Xing Q;Yao JJ;Wang YB;Song GR;Guo HS;Sun GH;Zhang YH;Li H;Du JL
研究背景硒蛋白S（Selenoprotein S，SelS）是一种跨膜蛋白，在肝脏、骨骼肌、脂肪组织、胰岛、肾脏和血管中均有表达。除跨膜定位外，SelS还可从肝癌HepG 2细胞中分泌（但不包括L 6骨骼肌细胞、3 T3-L1脂肪细胞、Min 6胰腺β细胞和人胚肾293细胞），并已在一些人类受试者的血清中检测到，检出率为31.1%。这些结果证明血清SelS是由肝细胞分泌的。然而，血管表达的SelS是否可以分泌还没有报道。SelS在糖尿病（DM）和动脉粥样硬化（AS）的发病机制和进展中起着不同的作用，但分泌型SelS与DM和大血管病变的关系尚不清楚。人主动脉血管平滑肌细胞（HA/VSMC）和人肝癌HepG 2细胞，其未转染或用指定质粒转染并浓缩用于蛋白质印迹。从158名患有或不患有2型DM（T2 DM）和/或AS的人类受试者中收集血清样品。血清SelS水平测定使用酶联免疫吸附试验。ResultsSecreted SelS仅在肝癌HepG 2细胞的上清液中检测到。158份血清样品中SelS的检出率为100%，平均水平为64.81ng/dl。单纯DM组血清SelS水平低于健康对照组（52.66 ± 20.53 vs 70.40 ± 21.38 ng/dl）。糖尿病合并SAS组和AS组血清SelS水平分别为67.73 ± 21.41 ng/dl和71.69 ± 27.00 ng/dl，均显著高于单纯糖尿病组。2型糖尿病与AS对血清SelS水平有交互作用（P = 0.002）。斯皮尔曼相关分析显示，血清SelS水平与空腹血糖呈负相关。血清SelS主要由肝细胞分泌。SelS在人血清中普遍存在，血清SelS水平与2型糖尿病及其大血管并发症有关。因此，调节肝脏和血清SelS水平可能成为预防和治疗糖尿病及其大血管并发症的新策略。
BackgroundSelenoprotein S (SelS) is a transmembrane protein that is expressed in the liver, skeletal muscle, adipose tissue, pancreatic islets, kidney, and blood vessels. In addition to its transmembrane localization, SelS is also secreted from hepatoma HepG2 cells (but not L6 skeletal muscle cells, 3T3-L1 adipocytes, Min6 pancreatic β cells and human embryonic kidney 293 cells) and has been detected in the serum of some human subjects, with a detection rate of 31.1 %. These findings prove that serum SelS is secreted by hepatocytes. However, whether vascularly expressed SelS can be secreted has not been reported. Transmembrane SelS has been suggested to play different roles in the pathogenesis and progression of diabetes mellitus (DM) and atherosclerosis (AS), but the association of secreted SelS with DM and macroangiopathy remains unclear.Research design and methodsSupernatants were collected from human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HA/VSMCs) and human hepatoma HepG2 cells that were untransfected or transfected with the indicated plasmid and concentrated for western blotting. Serum samples were collected from 158 human subjects with or without type 2 DM (T2DM) and/or AS. Serum SelS levels were measured using an enzyme-linked immunosorbent assay.ResultsSecreted SelS was only detected in the supernatants of hepatoma HepG2 cells. The SelS detection rate among the 158 human serum samples was 100 %, and the average SelS level was 64.81 ng/dl. The serum SelS level in the isolated DM subjects was lower than the level in the healthy control subjects (52.66 ± 20.53 vs 70.40 ± 21.38 ng/dl). The serum SelS levels in the DM complicated with SAS subjects (67.73 ± 21.41 ng/dl) and AS subjects (71.69 ± 27.00 ng/dl) were significantly increased compared with the serum SelS level in the isolated DM subjects. There was a positive interaction effect between T2DM and AS on the serum SelS level (P = 0.002). Spearman correlation analysis showed that the serum SelS level was negatively correlated with fasting plasma glucose.ConclusionsVascular endothelial and vascular smooth muscle cells could not secrete SelS. Serum SelS was primarily secreted by hepatocytes. SelS was universally detected in human serum samples, and the serum SelS level was associated with T2DM and its macrovascular complications. Thus, regulating liver and serum SelS levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications.