EGFL6 is increasingly expressed in human obesity and promotes proliferation of adipose tissue-derived stromal vascular cells
EGFL6 is increasingly expressed in human obesity and promotes proliferation of adipose tissue-derived stromal vascular cells
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DOI：
10.1007/s11010-010-0521-7
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发表时间：
2010-10-01
影响因子：
4.3
通讯作者：
Neubauer, Heike
中科院分区：
文献类型：
--
作者：
Oberauer, Rupert;Rist, Wolfgang;Neubauer, Heike
随着肥胖率的增加将2型糖尿病和心血管疾病的发病率推高到流行水平，了解脂肪组织扩张的生物学是当前研究的重点。脂肪组织分泌蛋白的鉴定和鉴定可以进一步深入了解脂肪组织的功能，并可能有助于在治疗上影响肥胖和相关代谢紊乱的发展。在本研究中，我们鉴定了人表皮生长因子样域多重-6(EGFL6)是一种脂肪组织分泌蛋白。EGFL6在人皮下脂肪组织中的表达随着肥胖的增加而显着增加，减肥后表达下降。此外，随着人前脂肪细胞的体外分化，EGFL6的表达和分泌增加，提示成熟脂肪细胞是EGFL6的主要来源。EGFL6含有表皮生长因子(EGF)样重复序列、精氨酸-甘氨酸-天冬氨酸(RGD)整合素结合基序、麦弗林、A5蛋白和受体蛋白-酪氨酸磷酸酶MU(MAM)结构域，是一种细胞外基质蛋白。重组人EGFL6蛋白以RGD依赖的方式介导人脂肪组织来源的基质血管细胞(AD-SVC)的细胞黏附。流式细胞仪分析显示该蛋白与AD-SVC细胞表面特异性结合，这种结合主要是由EGF样重复序列介导的。MTS法和[C-14]-胸腺嘧啶核苷掺入法检测重组EGFL6对人AD-SVC增殖的促进作用。这些结果表明，人EGFL6是一种脂肪组织旁分泌/自分泌生长因子，在肥胖中表达上调，并可能参与脂肪组织的扩张和肥胖的发生发展。
With increasing rates of obesity driving the incidence of type 2 diabetes and cardiovascular diseases to epidemic levels, understanding of the biology of adipose tissue expansion is a focus of current research. Identification and characterization of secreted proteins of the adipose tissue could provide further insights into the function of adipose tissue and might help to therapeutically influence the development of obesity and associated metabolic disorders. In the present study, we identified human epidermal growth factor-like domain multiple-6 (EGFL6) as an adipose tissue-secreted protein. EGFL6 expression in human subcutaneous adipose tissue significantly increased with obesity and decreased after weight loss. Further, expression and secretion of EGFL6 increased with in vitro differentiation of human preadipocytes, suggesting that mature adipocytes are the main source of EGFL6. Containing epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) integrin binding motif and a mephrin, A5 protein and receptor protein-tyrosine phosphatase mu (MAM) domain, EGFL6 was suggested to be an extra-cellular matrix protein. Recombinant human EGFL6 protein mediated cell adhesion of human adipose tissue-derived stromal vascular cells (AD-SVC) in an RGD-dependent manner. FACS analyses revealed specific binding of the protein to the cell surface of AD-SVC with the binding being predominantly mediated by the EGF-like repeats. Recombinant EGFL6 enhanced proliferation of human AD-SVC as measured by MTS assay and [C-14]-thymidine incorporation. These results indicate that human EGFL6 is a paracrine/autocrine growth factor of adipose tissue up-regulated in obesity and potentially involved in the process of adipose tissue expansion and the development of obesity.