The human amniotic fluid stem cell secretome triggers intracellular Ca2+ oscillations, NF-κB nuclear translocation and tube formation in human endothelial colony-forming cells.
J Cell Mol Med
; 25(16): 8074-8086, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34288391
ABSTRACT
Second trimester foetal human amniotic fluid-derived stem cells (hAFS) have been shown to possess remarkable cardioprotective paracrine potential in different preclinical models of myocardial injury and drug-induced cardiotoxicity. The hAFS secretome, namely the total soluble factors released by cells in their conditioned medium (hAFS-CM), can also strongly sustain in vivo angiogenesis in a murine model of acute myocardial infarction (MI) and stimulates human endothelial colony-forming cells (ECFCs), the only truly recognized endothelial progenitor, to form capillary-like structures in vitro. Preliminary work demonstrated that the hypoxic hAFS secretome (hAFS-CMHypo ) triggers intracellular Ca2+ oscillations in human ECFCs, but the underlying mechanisms and the downstream Ca2+ -dependent effectors remain elusive. Herein, we found that the secretome obtained by hAFS undergoing hypoxic preconditioning induced intracellular Ca2+ oscillations by promoting extracellular Ca2+ entry through Transient Receptor Potential Vanilloid 4 (TRPV4). TRPV4-mediated Ca2+ entry, in turn, promoted the concerted interplay between inositol-1,4,5-trisphosphate- and nicotinic acid adenine dinucleotide phosphate-induced endogenous Ca2+ release and store-operated Ca2+ entry (SOCE). hAFS-CMHypo -induced intracellular Ca2+ oscillations resulted in the nuclear translocation of the Ca2+ -sensitive transcription factor p65 NF-κB. Finally, inhibition of either intracellular Ca2+ oscillations or NF-κB activity prevented hAFS-CMHypo -induced ECFC tube formation. These data shed novel light on the molecular mechanisms whereby hAFS-CMHypo induces angiogenesis, thus providing useful insights for future therapeutic strategies against ischaemic-related myocardial injury.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Cálcio
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NF-kappa B
/
Meios de Cultivo Condicionados
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Células Endoteliais
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Secretoma
/
Líquido Amniótico
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália