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

José Luis Torán, Susana Aguilar, Juan Antonio López, Carlos Torroja, Juan Antonio Quintana, Cesar Santiago, José Luis Abad, Patricia Gomes-Alves, Andrés Gonzalez, Juan Antonio Bernal, Luis Jesús Jiménez-Borreguero, Paula Marques Alves, Luis R-Borlado, Jesús Vázquez, Antonio Bernad

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number12490
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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