RT Journal Article
T1 Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1
A1 Matilla, Lara
A1 Arrieta, Vanessa
A1 Jover, Eva
A1 García-Peña, Amaia
A1 Martínez Martínez, Ernesto
A1 Sadaba, Rafael
A1 Álvarez, Virginia
A1 Navarro, Adela
A1 Fernández-Celis, Amaya
A1 Gainza, Alicia
A1 Santamaria, Enrique
A1 Fernandez Irigoyen, Joaquín
A1 Rossignol, Patrick
A1 Zannad, Faiez
A1 López Andrés, Natalia
AB Circulating levels of soluble interleukin 1 receptor-like 1 (sST2) are increased in heart failure and associated with poor outcome, likely because of the activation of inflammation and fibrosis. We investigated the pathogenic role of sST2 as an inductor of cardiac fibroblasts activation and collagen synthesis. The effects of sST2 on human cardiac fibroblasts was assessed using proteomics and immunodetection approaches to evidence the upregulation of neuropilin-1 (NRP-1), a regulator of the profibrotic transforming growth factor (TGF)-β1. In parallel, sST2 increased fibroblast activation, collagen and fibrosis mediators. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) restored NRP-1 levels and blocked profibrotic effects induced by sST2. In NRP-1 knockdown cells, sST2 failed to induce fibroblast activation and collagen synthesis. Exogenous NRP-1 enhanced cardiac fibroblast activation and collagen synthesis via NF-κB. In a pressure overload rat model, sST2 was elevated in association with cardiac fibrosis and was positively correlated with NRP-1 expression. Our study shows that sST2 induces human cardiac fibroblasts activation, as well as the synthesis of collagen and profibrotic molecules. These effects are mediated by NRP-1. The blockade of NF-κB restored NRP-1 expression, improving the profibrotic status induced by sST2. These results show a new pathogenic role for sST2 and its mediator, NRP-1, as cardiac fibroblast activators contributing to cardiac fibrosis.
PB MDPI
SN 2073-4409
YR 2020
FD 2020-06-20
LK https://hdl.handle.net/20.500.14352/8372
UL https://hdl.handle.net/20.500.14352/8372
LA eng
NO Instituto de Salud Carlos III (ISCIII)/FEDER
NO Instituto de Salud Carlos III (ISCIII)
NO ANR (France)
DS Docta Complutense
RD 9 abr 2025