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On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2023-08-08
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Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway
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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-;β;1 (TGF;-;β;1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-;β;1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF;-;β;1 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-;β;1 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-;β;1. In summary, activation of the TGF-;β;1/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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Shenjian LUO, Zhi YANG, Ruxin CHEN, Danming YOU, Fei TENG, Youwen YUAN, Wenhui LIU, Jin LI, Huijie ZHANG. Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway[J]. Journal of Zhejiang University Science B, 2023, 24(8): 682-697.
@article{title="Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway",
author="Shenjian LUO, Zhi YANG, Ruxin CHEN, Danming YOU, Fei TENG, Youwen YUAN, Wenhui LIU, Jin LI, Huijie ZHANG",
journal="Journal of Zhejiang University Science B",
volume="24",
number="8",
pages="682-697",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200506"
}
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%A Shenjian LUO
%A Zhi YANG
%A Ruxin CHEN
%A Danming YOU
%A Fei TENG
%A Youwen YUAN
%A Wenhui LIU
%A Jin LI
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A1 - Danming YOU
A1 - Fei TENG
A1 - Youwen YUAN
A1 - Wenhui LIU
A1 - Jin LI
A1 - Huijie ZHANG
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%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2200506
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