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Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B ; (12): 682-697, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1010563
ABSTRACT
Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fibrosis / Transducción de Señal / Receptores de Citocinas / Sistema de Señalización de MAP Quinasas / Proteína Quinasa 3 Activada por Mitógenos / Modelos Animales de Enfermedad / Factor de Crecimiento Transformador beta1 / Fibroblastos / Infarto del Miocardio Límite: Animales / Humanos Idioma: Inglés Revista: Journal of Zhejiang University. Science. B Año: 2023 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fibrosis / Transducción de Señal / Receptores de Citocinas / Sistema de Señalización de MAP Quinasas / Proteína Quinasa 3 Activada por Mitógenos / Modelos Animales de Enfermedad / Factor de Crecimiento Transformador beta1 / Fibroblastos / Infarto del Miocardio Límite: Animales / Humanos Idioma: Inglés Revista: Journal of Zhejiang University. Science. B Año: 2023 Tipo del documento: Artículo