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Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1

Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, 31008 Pamplona, Spain
Departamento de Fisiología, Facultad Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, 28040 Madrid, Spain
Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Institute for Health Research, Universidad Pública de Navarra, IdiSNA, 31008 Pamplona, Spain
INSERM, Centre d’Investigations Cliniques-Plurithématique 1433, UMR 1116, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, 54035 Nancy, France
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Cells 2020, 9(7), 1667;
Received: 16 May 2020 / Revised: 21 June 2020 / Accepted: 7 July 2020 / Published: 10 July 2020
(This article belongs to the Special Issue Cells in Cardiovascular Disease)
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. View Full-Text
Keywords: sST2; neuropilin-1; collagen; fibroblast activation; NF-κB sST2; neuropilin-1; collagen; fibroblast activation; NF-κB
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MDPI and ACS Style

Matilla, L.; Arrieta, V.; Jover, E.; Garcia-Peña, A.; Martinez-Martinez, E.; Sadaba, R.; Alvarez, V.; Navarro, A.; Fernandez-Celis, A.; Gainza, A.; Santamaria, E.; Fernandez-Irigoyen, J.; Rossignol, P.; Zannad, F.; Lopez-Andres, N. Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1. Cells 2020, 9, 1667.

AMA Style

Matilla L, Arrieta V, Jover E, Garcia-Peña A, Martinez-Martinez E, Sadaba R, Alvarez V, Navarro A, Fernandez-Celis A, Gainza A, Santamaria E, Fernandez-Irigoyen J, Rossignol P, Zannad F, Lopez-Andres N. Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1. Cells. 2020; 9(7):1667.

Chicago/Turabian Style

Matilla, Lara, Vanessa Arrieta, Eva Jover, Amaia Garcia-Peña, Ernesto Martinez-Martinez, Rafael Sadaba, Virginia Alvarez, Adela Navarro, Amaya Fernandez-Celis, Alicia Gainza, Enrique Santamaria, Joaquín Fernandez-Irigoyen, Patrick Rossignol, Faiez Zannad, and Natalia Lopez-Andres. 2020. "Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1" Cells 9, no. 7: 1667.

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