HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells
HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells
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DOI：
10.1186/1742-4690-8-40
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发表时间：
2011-05-25
期刊：
影响因子：
3.3
通讯作者：
Re, Maria Carla
中科院分区：
文献类型：
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作者：
Gibellini, Davide;Alviano, Francesco;Re, Maria Carla
背景资料：HIV感染引起进行性免疫缺陷的发作，并且还损害几种其它器官和组织，例如CNS、肾、心脏、血管、脂肪组织和骨。特别是，艾滋病毒感染与心血管疾病发病率增加和血管结构紊乱有关，而没有传统的危险因素。最近的表征多能间充质细胞在血管壁中，参与调节细胞内稳态，表明这些细胞可能被认为是艾滋病毒发病机制的目标。本文研究了HIV-1与血管壁驻留的人间充质干细胞（MSCs）之间的相互作用。结果：经典的R5和X4 HIV-1实验室毒株攻击MSCs，证明这些毒株能够进入宿主细胞基因组并整合其逆转录的前病毒DNA。随后的实验表明，HIV-1菌株和重组gp 120引起了可靠的增加，在亚融合的MSC细胞凋亡。由于血管壁间充质干细胞是多能细胞，可以分化成几个细胞谱系，我们挑战HIV-1株和gp 120对分化成脂肪和内皮细胞的间充质干细胞。我们的实验表明，脂肪形成增加，特别是通过上调的过氧化物酶体增殖物激活受体γ活性，而内皮细胞分化诱导的血管内皮细胞生长因子治疗受损与下调的内皮标志物，如vWF，Flt-1和KDR的表达。这些病毒在MSC的生存和成脂或内皮细胞分化的影响进行了处理的CD 4阻断表明CD 4/gp 120的相互作用在这种情况下的一个重要作用。结论：HIV相关的紊乱MSC的生存和分化可能表明HIV感染和gp 120在受损的血管内稳态和HIV感染患者中观察到的血管损伤的成因的直接作用。
Background: HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs).Results: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR gamma activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context.Conclusions: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients.