Martínez Martínez, ErnestoIbarrola, JaimeFernández Celis, AmayaSantamaria, EnriqueFernández Irigoyen, JoaquínRossignol, PatrickJaisser, FredericLópez Andrés, Natalia2025-01-302025-01-302017-09-22Martínez-Martínez E, Ibarrola J, Fernández-Celis A, Santamaria E, Fernández-Irigoyen J, Rossignol P, Jaisser F, López-Andrés N. Differential Proteomics Identifies Reticulocalbin-3 as a Novel Negative Mediator of Collagen Production in Human Cardiac Fibroblasts. Sci Rep. 2017 Sep 22;7(1):12192.10.1038/s41598-017-12305-7https://hdl.handle.net/20.500.14352/117101FIBROTARGETS projectCardiac 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article2045-2322https://doi.org/10.1038/s41598-017-12305-728939891https://www.nature.com/articles/s41598-017-12305-7open access612Cardiovascular biologyMechanisms of diseaseSistema cardiovascular24 Ciencias de la Vida