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国家自然科学基金(30770887)

作品数:3 被引量:22H指数:3
相关作者:谢小洁胡新央王建安刘先宝王雯霞更多>>
相关机构:浙江大学医学院附属第二医院更多>>
发文基金:国家自然科学基金更多>>
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神经生长因子促进骨髓间充质干细胞血管新生能力被引量:3
2011年
目的探讨神经生长因子(NGF)对大鼠骨髓间充质干细胞(MSCs)血管新生能力的影响,及其可能的作用机制。方法 24孔板中matrigel铺板后种植MSCs,用不同浓度的NGF(0、25、50、100、200 ng/mL)处理细胞24 h,观察MSCs体外形成管腔样结构的能力,同时用特异性NGF酪氨酸受体(TrkA)阻滞剂K-252a阻断受体,观察K-252a对NGF促MSCs血管新生的抑制作用。应用Western印迹法比较NGF处理组MSCs与对照组MSCs的血管内皮生长因子(VEGF)的表达情况。结果不同浓度的NGF均有促血管新生的作用,其中NGF 50 ng/mL促进MSCs血管新生的能力最强,该组MSCs形成的管腔长度为对照组的2.24倍(P=0.01)。NGF处理组MSCs的VEGF表达情况与对照组的差异无统计学意义(P>0.05)。K-252a阻断TrkA受体后,NGF促进MSCs管腔样结构形成的能力明显减弱。结论 NGF可以促进MSCs在体外matrigel中的血管新生能力,其作用机制可能与激活TrkA受体有关。
王雯霞胡新央谢小洁刘先宝王建安
关键词:神经生长因子骨髓间充质干细胞血管新生
Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways被引量:12
2010年
Mesenchymal stem cell (MSC) transplantation has shown a therapeutic potential to repair the ischemic and infracted myocardium, but the effects are limited by the apoptosis and loss of donor cells in host cardiac microenvironment. The aim of this study is to explore the cytoprotection of heat shock protein 90 (Hsp90) against hypoxia and serum deprivation-induced apoptosis and the possible mechanisms in rat MSCs. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric analysis with annexin V/PI staining. The gene expression of Toll-like receptor-4 (TLR-4) and V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ErbB2) was detected by real-time poly- merase chain reaction (PCR). The protein levels of cleaved caspase-3, Bcl-2, Bcl-xL, Bax, totaI-ERK, phospho-ERK, totaI-Akt, phospho-Akt, and Hsp90 were detected by Western blot. The production of nitric oxide was measured by spectrophotometric assay. Hsp90 improves MSC viability and protects MSCs against apoptosis induced by serum deprivation and hypoxia. The protective role of Hsp90 not only elevates Bcl-2/Bax and Bcl-xL/Bax expression and attenuates cleaved caspase-3 expression via down-regulating membrane TLR-4 and ErbB2 receptors and then ac- tivating their downstream PI3K/Akt and ERK1/2 pathways, but also enhances the paracrine effect of MSCs. These findings demonstrated a novel and effective treatment strategy against MSC apoptosis in cell transplantation.
Feng GAOXin-yang HUXiao-jie XIEQi-yuan XUYa-ping WANGXian-bao LIUMei-xiang XIANGYong SUNJian-an WANG
关键词:HYPOXIA
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