RT Journal Article
T1 Differential Proteomics Identifies Reticulocalbin-3 as a Novel Negative Mediator of Collagen Production in Human Cardiac Fibroblasts
A1 Martínez Martínez, Ernesto
A1 Ibarrola, Jaime
A1 Fernández Celis, Amaya
A1 Santamaria, Enrique
A1 Fernández Irigoyen, Joaquín
A1 Rossignol, Patrick
A1 Jaisser, Frederic
A1 López Andrés, Natalia
AB 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.
PB Springer
YR 2017
FD 2017-09-22
LK https://hdl.handle.net/20.500.14352/117101
UL https://hdl.handle.net/20.500.14352/117101
LA eng
NO Martínez-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.
NO FIBROTARGETS project
NO Instituto de Salud Carlos III
NO Unión Europea
NO COST ADMIRE network
DS Docta Complutense
RD 30 mar 2026