Clarkin Claire E, Mahmoud Marwa, Liu Bo, Sobamowo Emmanuel O, King Aileen, Arthur Helen, Jones Peter M, Wheeler-Jones Caroline P
Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine, Kings College London, London, SE1 1UL, UK.
Centre for Biological Sciences, University of Southampton, Building 85/Life Sciences, University Road, Southampton, SO17 1BJ, UK.
BMC Res Notes. 2016 Jul 25;9:362. doi: 10.1186/s13104-016-2142-z.
Endoglin/CD105 is an auxiliary receptor for transforming growth factor-β with established roles in vascular remodelling. It has recently been shown that heterozygous endoglin deficiency in mice decreases insulin secretion in an animal model of obesity, highlighting a potential role for endoglin in the regulation of islet function. We have previously identified two different populations of endoglin expressing cells in human and mouse islets which are: (i) endothelial cells (ECs) and (ii) islet mesenchymal stromal cells. The contribution of islet EC endoglin expression to islet development and sensitivity to VEGF is unknown and is the focus of this study.
In vitro culture of mouse islets with VEGF164 for 48 h increased endoglin mRNA levels above untreated controls but VEGF did not modulate VEGFR2, CD31 or CD34 mRNA expression or islet viability. Removal of EC-endoglin expression in vivo reduced islet EC area but had no apparent effect on islet size or architecture.
EC-specific endoglin expression in islets is sensitive to VEGF and plays partial roles in driving islet vascular development, however such regulation appears to be distinct to mechanisms required to modulate islet viability and size.
内皮糖蛋白/CD105是转化生长因子-β的辅助受体，在血管重塑中发挥既定作用。最近研究表明，在肥胖动物模型中，小鼠内皮糖蛋白杂合性缺乏会降低胰岛素分泌，这突出了内皮糖蛋白在胰岛功能调节中的潜在作用。我们之前已在人和小鼠胰岛中鉴定出两种不同的内皮糖蛋白表达细胞群体，即：（i）内皮细胞（ECs）和（ii）胰岛间充质基质细胞。胰岛EC内皮糖蛋白表达对胰岛发育及对VEGF敏感性的贡献尚不清楚，这也是本研究的重点。
用VEGF164体外培养小鼠胰岛48小时，内皮糖蛋白mRNA水平高于未处理的对照组，但VEGF未调节VEGFR2、CD31或CD34的mRNA表达或胰岛活力。体内去除EC-内皮糖蛋白表达可减少胰岛EC面积，但对胰岛大小或结构无明显影响。
胰岛中EC特异性内皮糖蛋白表达对VEGF敏感，在驱动胰岛血管发育中起部分作用，然而这种调节似乎与调节胰岛活力和大小所需的机制不同。
