CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome

Studies in recent years have established that the principal effects in cardiac cell therapy are associated with paracrine/autocrine factors. We combined several complementary techniques to define human cardiac progenitor cell (CPC) secretome constituted by 914 proteins/genes; 51% of these are associ...

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Bibliographic Details
Published in:Scientific reports 2017-10, Vol.7 (1), p.12490-14, Article 12490
Main Authors: Torán, José Luis, Aguilar, Susana, López, Juan Antonio, Torroja, Carlos, Quintana, Juan Antonio, Santiago, Cesar, Abad, José Luis, Gomes-Alves, Patricia, Gonzalez, Andrés, Bernal, Juan Antonio, Jiménez-Borreguero, Luis Jesús, Alves, Paula Marques, R-Borlado, Luis, Vázquez, Jesús, Bernad, Antonio
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Antibodies, Neutralizing - pharmacology
Antigens
Autocrine signalling
Cell Movement
Chemokine CXCL1 - genetics
Chemokine CXCL1 - metabolism
Chemokine CXCL6 - antagonists & inhibitors
Chemokine CXCL6 - genetics
Chemokine CXCL6 - metabolism
Chemokines
Culture Media, Conditioned - chemistry
Culture Media, Conditioned - metabolism
CXCR2 protein
Cytokines
Enzyme-linked immunosorbent assay
Fibroblasts
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - metabolism
Gene Expression Regulation
Growth factors
Heart
Heart diseases
Human Umbilical Vein Endothelial Cells - cytology
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Hypotheses
Interleukin 1
Interleukin 8
Interleukin-1 - genetics
Interleukin-1 - metabolism
Interleukin-8 - genetics
Interleukin-8 - metabolism
Leukocyte migration
Male
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - metabolism
Mesenchyme
Mice
Mice, Inbred C57BL
Myocardium - cytology
Myocardium - metabolism
Neovascularization, Physiologic - genetics
Paracrine Communication - genetics
Paracrine signalling
Progenitor cells
Proteins
Proteome - genetics
Proteome - metabolism
Proteomics
Receptors, Interleukin-8A - antagonists & inhibitors
Receptors, Interleukin-8A - genetics
Receptors, Interleukin-8A - metabolism
Receptors, Interleukin-8B - antagonists & inhibitors
Receptors, Interleukin-8B - genetics
Receptors, Interleukin-8B - metabolism
Research centers
Secretome
Signal Transduction
Skin
Stem cells
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
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Summary:Studies in recent years have established that the principal effects in cardiac cell therapy are associated with paracrine/autocrine factors. We combined several complementary techniques to define human cardiac progenitor cell (CPC) secretome constituted by 914 proteins/genes; 51% of these are associated with the exosomal compartment. To define the set of proteins specifically or highly differentially secreted by CPC, we compared human mesenchymal stem cells and dermal fibroblasts; the study defined a group of growth factors, cytokines and chemokines expressed at high to medium levels by CPC. Among them, IL-1, GROa (CXCL1), CXCL6 (GCP2) and IL-8 are examples whose expression was confirmed by most techniques used. ELISA showed that CXCL6 is significantly overexpressed in CPC conditioned medium (CM) (18- to 26-fold) and western blot confirmed expression of its receptors CXCR1 and CXCR2. Addition of anti-CXCL6 completely abolished migration in CPC-CM compared with anti-CXCR2, which promoted partial inhibition, and anti-CXCR1, which was inefficient. Anti-CXCL6 also significantly inhibited CPC CM angiogenic activity. In vivo evaluation also supported a relevant role for angiogenesis. Altogether, these results suggest a notable angiogenic potential in CPC-CM and identify CXCL6 as an important paracrine factor for CPC that signals mainly through CXCR2.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-11976-6