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

比较蛋白质组学分析揭示平滑肌祖细胞在细胞外基质产生中的作用

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作者:David Simper, Ursula Mayr, Carmen Urbich, Anna Zampetaki, Marianna Prokopi, Athanasios Didangelos, Angelika Saje, Michael Mueller, Ulrike Benbow, Andrew C Newby, Rolf Apweiler, Salman Rahman, Stefanie Dimmeler, Qingbo Xu, Manuel Mayr

Conclusions

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

Objective

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

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.

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