Pancreatic duct cells as a source of VEGF in mice.
Pancreatic duct cells as a source of VEGF in mice.
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DOI：
10.1007/s00125-014-3179-y
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发表时间：
2014-05
期刊：
影响因子：
8.2
通讯作者：
Gittes, George K.
中科院分区：
文献类型：
--
作者：
Xiao, Xiangwei;Prasadan, Krishna;Guo, Ping;El-Gohary, Yousef;Fischbach, Shane;Wiersch, John;Gaffar, Iljana;Shiota, Chiyo;Gittes, George K.
关键词：
血管内皮生长因子（VEGF）是胰腺正常发育、胰岛血管化和胰岛素分泌所必需的。在成人胰腺中，VEGF被认为主要由β细胞分泌。虽然人导管细胞先前已显示在培养物中以血管生成水平分泌VEGF，但一直缺乏VEGF合成和分泌的动力学分析以及这种导管VEGF在影响胰岛功能和生理学中的体内作用的阐明。我们分析了纯化的导管细胞独立制备的流式细胞仪，手术分离或激光捕获显微切割。我们在胰腺导管内输注系统中用Vegfa短发夹RNA（shRNA）感染导管细胞，并在体外和体内研究VEGF敲低对导管细胞的影响。胰管细胞表达高水平的Vegfa mRNA。与β细胞相比，导管细胞分泌的VEGF与细胞内VEGF的比例更高。作为生物测定，当单独培养时，人脐静脉内皮细胞形成的管状结构基本上检测不到，当与胰管细胞共培养时，管状结构的形成显著增加，但当与用Vegfa shRNA预处理的导管细胞共培养时，管状结构的形成显著减少。与单独移植的胰岛相比，在与导管细胞共移植的胰岛中检测到改善的血管形成和功能，但在与用Vegfa shRNA预处理的导管细胞共移植的胰岛中未检测到。用于移植的人胰岛制剂通常含有一些污染的导管细胞，我们的研究结果表明，胰岛制剂中导管细胞的存在可能会改善移植结果。
Vascular endothelial growth factor (VEGF) is essential for proper pancreatic development, islet vascularisation and insulin secretion. In the adult pancreas, VEGF is thought to be predominantly secreted by beta cells. Although human duct cells have previously been shown to secrete VEGF at angiogenic levels in culture, an analysis of the kinetics of VEGF synthesis and secretion, as well as elucidation of an in vivo role for this ductal VEGF in affecting islet function and physiology, has been lacking. We analysed purified duct cells independently prepared by flow cytometry, surgical isolation or laser-capture microdissection. We infected duct cells in vivo with Vegfa short hairpin RNA (shRNA) in an intrapancreatic ductal infusion system and examined the effect of VEGF knockdown in duct cells in vitro and in vivo. Pancreatic duct cells express high levels of Vegfa mRNA. Compared with beta cells, duct cells had a much higher ratio of secreted to intracellular VEGF. As a bioassay, formation of tubular structures by human umbilical vein endothelial cells was essentially undetectable when cultured alone and was substantially increased when co-cultured with pancreatic duct cells but significantly reduced when co-cultured with duct cells pretreated with Vegfa shRNA. Compared with islets transplanted alone, improved vascularisation and function was detected in the islets co-transplanted with duct cells but not in islets co-transplanted with duct cells pretreated with Vegfa shRNA. Human islet preparations for transplantation typically contain some contaminating duct cells and our findings suggest that the presence of duct cells in the islet preparation may improve transplantation outcomes.
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影响因子：
8.2
作者：
Iwashita, N.;Uchida, T.;Watada, H.
通讯作者：
Watada, H.
DOI：
10.1161/atvbaha.108.179663
发表时间：
2009-06-01
影响因子：
8.7
作者：
Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone
DOI：
10.1152/ajpendo.00321.2002
发表时间：
2003-01-01
影响因子：
5.1
作者：
Hara, M;Wang, XY;Bell, GI
通讯作者：
Bell, GI
影响因子：
5.3
作者：
Huez, I;Créancier, L;Prats, H
通讯作者：
Prats, H
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.