title: Analysis of pregnancy-associated plasma protein A production in human adult cardiac progenitor cells.
abstract: 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.
authors: Department of Gynaecology, Obstetrics and Urologic Sciences, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors: Piera
authors: P
authors: D'Elia
authors: Vittoria
authors: V
authors: Ionta
authors: Isotta
authors: I
authors: Chimenti
authors: Francesco
authors: F
authors: Angelini
authors: Fabio
authors: F
authors: Miraldi
authors: Alessandro
authors: A
authors: Pala
authors: Elisa
authors: E
authors: Messina
authors: Alessandro
authors: A
authors: Giacomello
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007118:Immunoassay; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000096:biosynthesis*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D011266:Pregnancy-Associated Plasma Protein-A