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人骨髓间充质干细胞来源的微小囊泡的蛋白质组学分析。

Proteomic analysis of microvesicles derived from human mesenchymal stem cells.

机构信息

Department of Laboratory Medicine, Yonsei University College of Medicine , 50 Yonsei-ro, Seodaemoon-gu, Seoul 120-752, Republic of Korea.

出版信息

J Proteome Res. 2012 Feb 3;11(2):839-49. doi: 10.1021/pr200682z. Epub 2011 Dec 28.


DOI:10.1021/pr200682z
PMID:22148876
Abstract

Mesenchymal stem cells (MSCs) have emerged as a promising means for treating degenerative or incurable diseases. Recent studies have shown that microvesicles (MVs) from MSCs (MSC-MVs) contribute to recovery of damaged tissues in animal disease models. Here, we profiled the MSC-MV proteome to investigate their therapeutic effects. LC-MS/MS analysis of MSC-MVs identified 730 MV proteins. The MSC-MV proteome included five positive and two variable known markers of MSCs, but no negative marker, as well as 43 surface receptors and signaling molecules controlling self-renewal and differentiation of MSCs. Functional enrichment analysis showed that cellular processes represented by the MSC-MV proteins include cell proliferation, adhesion, migration, and morphogenesis. Integration of MSC's self-renewal and differentiation-related genes and the proteome of MSC-conditioned media (MSC-CM) with the MSC-MV proteome revealed potential MV protein candidates that can be associated with the therapeutic effects of MSC-MVs: (1) surface receptors (PDGFRB, EGFR, and PLAUR); (2) signaling molecules (RRAS/NRAS, MAPK1, GNA13/GNG12, CDC42, and VAV2); (3) cell adhesion (FN1, EZR, IQGAP1, CD47, integrins, and LGALS1/LGALS3); and (4) MSC-associated antigens (CD9, CD63, CD81, CD109, CD151, CD248, and CD276). Therefore, the MSC-MV proteome provides a comprehensive basis for understanding the potential of MSC-MVs to affect tissue repair and regeneration.

摘要

间充质干细胞(MSCs)已成为治疗退行性或无法治愈疾病的有前途的手段。最近的研究表明,来自间充质干细胞的微泡(MSC-MVs)有助于在动物疾病模型中恢复受损组织。在这里,我们对 MSC-MV 蛋白质组进行了分析,以研究其治疗效果。LC-MS/MS 分析 MSC-MVs 鉴定出 730 种 MV 蛋白。MSC-MV 蛋白质组包括五个阳性和两个可变的已知 MSC 标志物,但没有阴性标志物,以及 43 个表面受体和信号分子,这些受体和信号分子控制着 MSC 的自我更新和分化。功能富集分析表明,MSC-MV 蛋白所代表的细胞过程包括细胞增殖、粘附、迁移和形态发生。将 MSC 的自我更新和分化相关基因与 MSC 条件培养基(MSC-CM)的蛋白质组与 MSC-MV 蛋白质组整合,揭示了可能与 MSC-MVs 治疗效果相关的潜在 MV 蛋白候选物:(1)表面受体(PDGFRB、EGFR 和 PLAUR);(2)信号分子(RRAS/NRAS、MAPK1、GNA13/GNG12、CDC42 和 VAV2);(3)细胞粘附(FN1、EZR、IQGAP1、CD47、整合素和 LGALS1/LGALS3);和(4)MSC 相关抗原(CD9、CD63、CD81、CD109、CD151、CD248 和 CD276)。因此,MSC-MV 蛋白质组为理解 MSC-MVs 影响组织修复和再生的潜力提供了全面的基础。

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