Vascular endothelial growth factor over-expressed mesenchymal stem cells-conditioned media ameliorate palmitate-induced diabetic endothelial dysfunction through PI-3K/AKT/m-TOR/eNOS and p38/MAPK signaling pathway

被引:29
作者
Xu, Tianwei [1 ]
Lv, Zhengbing [2 ]
Chen, Qiuhua [3 ]
Guo, Min [1 ]
Wang, Xufang [1 ]
Huang, Fengjie [1 ]
机构
[1] China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing, Jiangsu, Peoples R China
[2] Zhejiang Sci Tech Univ, Sch Life Sci, Hangzhou, Zhejiang, Peoples R China
[3] Nanjing Univ Tradit Chinese Med, Intens Care Unit, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Vascular endothelial growth factor; Mesenchymal stem cells conditioned medium; Pancreatic islet endothelial cells; PI-3K/AKT/m-TOR/eNOS; P38/MAPK; FACTOR-A; VEGF-A; PANCREATIC-ISLETS; PROLIFERATION; AKT; INFLAMMATION; PREVALENCE; PROTECTS; MOLECULE; ADHESION;
D O I
10.1016/j.biopha.2018.06.129
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
In the pathogenesis of diabetes mellitus (DM), islet microvasculares are severely damaged due to glucolipotoxicity and other reasons. Vascular endothelial growth factor (VEGF) is an indispensable and specific angiogenic factor in the pathogenesis and treatment of diabetic islet microvascular disease. Mesenchymal stem cells (MSCs) are regarded as a promising treatment of diabetes because of their immunosuppressive effect and multipotential differentiation potency. In this study, we tested whether MSCs over-expressing VEGF conditioned medium (MSC-VEGF-CM) could ameliorate pancreatic islet endothelial cells (MS-1) dysfunction induced by a common diabetic inducer palmitate (PA). We found that cell survival and migration were restrained by PA and partly repaired by the pro-protected of MSC-VEGF-CM. Meanwhile, PI-3K/AKT/m-TOR/eNOS and p38/MAPK signaling pathways were also upregulated. Though apoptosis-related proteins, caspase-3 and caspase-9, had no significantly suppressed between MSC-VEGF-CM and MSC-CM alone, the expression levels of vascular surface factors such as CD31, VE-cadherin, occludin and ICAM-1, were remarkably up-regulated by the pro-protected of MSC-VEGF-CM. Our data suggested that MSC-VEGF-CM had therapeutic effect on the PA-induced dysfunction through the re-activation of PI-3K/AKT/m-TOR/eNOS and p38/MAPK signaling pathways.
引用
收藏
页码:491 / 498
页数:8
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