比较蛋白质组学分析揭示了平滑肌祖细胞在细胞外基质产生中的作用。

Comparative proteomics profiling reveals role of smooth muscle progenitors in extracellular matrix production.

机构信息

Department of Cardiology, Phoenix VA Health Care System, Phoenix, AZ, USA.

出版信息

Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1325-32. doi: 10.1161/ATVBAHA.110.204651. Epub 2010 Apr 29.

Abstract

OBJECTIVE

Recent studies on cardiovascular progenitors have led to a new appreciation that paracrine factors may support the regeneration of damaged tissues.

METHODS AND RESULTS

We used a shotgun proteomics strategy to compare the secretome of peripheral blood-derived smooth muscle progenitors (SPCs) with human aortic smooth muscle cells. The late-outgrowth SPCs produced fewer proteolytic enzymes and inflammatory cytokines and showed reduced invasive capacity. Similar to smooth muscle cells, SPCs secreted extracellular matrix. However, SPCs produced different matrix proteins, as evidenced by the truncation of proangiogenic domains in collagen alpha-1 (I) and increased production of periostin. Moreover, SPCs retained serum proteins, including proteoglycans, regulating collagen assembly; and pigment epithelium-derived factor, a potent inhibitor of angiogenesis. As a functional consequence, their conditioned medium was less angiogenic, as demonstrated by endothelial tube formation assays in vitro and implantation of Matrigel plugs into nude, severe combined immunodeficient mice (NOD/SCID).

CONCLUSIONS

The present study represents an important conceptual development, suggesting that SPCs may contribute to extracellular matrix production.

摘要

目的

最近有关心血管祖细胞的研究使人们认识到旁分泌因子可能有助于受损组织的再生。

方法和结果

我们使用一种鸟枪法蛋白质组学策略,比较了外周血衍生的平滑肌祖细胞(SPCs)与人类主动脉平滑肌细胞的分泌组。晚期生长的 SPCs 产生较少的蛋白水解酶和炎症细胞因子,侵袭能力降低。与平滑肌细胞相似,SPCs 分泌细胞外基质。然而,SPCs 产生了不同的基质蛋白,这一点可从胶原 alpha-1(I)的血管生成结构域缺失和骨膜蛋白的产生增加得到证明。此外,SPCs 保留了调节胶原组装的血清蛋白,包括蛋白聚糖;以及色素上皮衍生因子,一种有效的血管生成抑制剂。作为一个功能结果,它们的条件培养基的血管生成能力降低,这可以通过体外内皮管形成试验和将 Matrigel 塞植入裸鼠、严重联合免疫缺陷小鼠(NOD/SCID)中得到证明。

结论

本研究代表了一个重要的概念发展,表明 SPCs 可能有助于细胞外基质的产生。

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