{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Luo S"],"funding":["the National Key Research and Development Project of China","the China Postdoctoral Science Foundation","the National Natural Science Foundation of China"],"pagination":["682-697"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10423965"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(8)"],"pubmed_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 <i>CRLF1</i> 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 <i>CRLF1</i> were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. <i>CRLF1</i> overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of <i>CRLF1</i> 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 <i>CRLF1</i> up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased <i>CRLF1</i> 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."],"journal":["Journal of Zhejiang University. Science. B"],"pubmed_title":["Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway."],"pmcid":["PMC10423965"],"funding_grant_id":["2021M691459 and 2022T150299","82100255 and 81970736","2018YFA0800404"],"pubmed_authors":["Yang Z","Li J","Zhang H","You D","Teng F","Luo S","Chen R","Yuan Y","Liu W"],"additional_accession":[]},"is_claimable":false,"name":"Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway.","description":"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 <i>CRLF1</i> 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 <i>CRLF1</i> were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. <i>CRLF1</i> overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of <i>CRLF1</i> 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 <i>CRLF1</i> up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased <i>CRLF1</i> 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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2025-04-05T15:47:22.535Z","creation":"2025-04-05T15:47:22.535Z"},"accession":"S-EPMC10423965","cross_references":{"pubmed":["37551555"],"doi":["10.1631/jzus.B2200506","10.1631/jzus.b2200506"]}}