Department of Gynaecology, Obstetrics and Urologic Sciences, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Biomed Res Int. 2013;2013:190178. doi: 10.1155/2013/190178. Epub 2013 Nov 10.
IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology.
胰岛素样生长因子结合蛋白（IGFBPs）及其蛋白酶在多种组织中调节 IGFs 的生物利用度。妊娠相关血浆蛋白 A（PAPP-A）是一种通过切割 IGFBP2、4 和 5 起作用的蛋白酶，调节 IGFs 的局部生物利用度。我们之前已经表明，IGFs 和 IGFBPs 由人成体心脏祖细胞（haCPCs）产生，并且 IGF-1 在 CPCs 心脏细胞治疗中发挥旁分泌治疗作用。通过免疫荧光和酶联免疫吸附试验，我们首先报告 PAPP-A 由 haCPCs 以惊人的高量产生和分泌。特别是，具有酶活性的同源二聚体 PAPP-A 以相关浓度分泌在 haCPC 条件培养基中，而在相同的培养基中不能检测到无酶活性的 PAPPA/proMBP 复合物。此外，我们表明，同源二聚体 PAPP-A 和 proMBP 均可作为细胞相关物检测到，这表明先前在细胞表面描述的复合物形成不易发生，从而对 IGF 信号产生积极影响。因此，我们的结果强烈支持 PAPP-A 在 CPCs 生物学中的 IGFs/IGFBPs/PAPP-A 轴中的重要性。
