Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-12305-7
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Funding
- Instituto de Salud Carlos III-FEDER [CP13/00221]
- Fondo de Investigaciones Sanitarias [PI15/02160]
- FIBROTARGETS [602904]
- COST ADMIRE network [BM1301]
- RHU [ANR-15-RHUS-0004]
- ISCIII [PT13/0001]
- FEDER
- ISCIII
- Agence Nationale de la Recherche (ANR) [ANR-15-RHUS-0004] Funding Source: Agence Nationale de la Recherche (ANR)
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Cardiac fibrosis is characterized by an excessive accumulation of extracellular matrix components, including collagens. Galectin-3 (Gal-3) and Cardiotrophin-1 (CT-1) are two profibrotic molecules that mediate Aldosterone (Aldo)-induced cardiac fibrosis. However the underlying mechanisms are not well defined. Our aim is to characterize changes in the proteome of human cardiac fibroblasts treated with Aldo, Gal-3 or CT-1 to identify new common proteins that might be new therapeutic targets in cardiac fibrosis. Using a quantitative proteomic approach in human cardiac fibroblasts, our results show that Aldo, Gal-3 and CT-1 modified the expression of 30, 17 and 89 proteins respectively, being common the reticulocalbin (RCN) family members. RCN-3 down-regulation triggered by Aldo, Gal-3 and CT-1 was verified. Treatment with recombinant RCN-3 decreased collagens expression in human cardiac fibroblasts through Akt phosphorylation. Interestingly, CRISPR/Cas9-mediated activation of RCN-3 decreased collagen production in human cardiac fibroblasts. In addition, recombinant RCN-3 blocked the profibrotic effects of Aldo, Gal-3 and CT-1. Interestingly, RCN-3 blunted the increase in collagens expression induced by other profibrotic stimuli, angiotensin II, in human cardiac fibroblasts. Our results suggest that RCN-3 emerges as a new potential negative regulator of collagen production and could represent a therapeutic target in the context of cardiac fibrosis.
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