关键词:
Gene expression
Myocardial infarction
Fibroblasts
Notch signaling
Fibrosis
Inflammation
STAT signaling
Protein expression
摘要:
Objective Investigate the role of the Neurogenic locus notch homolog protein 1 (NOTCH1) signaling pathway in Diffuse large B-cell lymphoma (DLBCL)-related heart pathogenesis. Methods Utilize R (version 4.2.1) to retrieve DLBCL and myocardial infarction datasets from the GEO database, normalize data with limma, perform differential analysis and GO analysis with GOplot, and visualize findings with ggplot2. Various assays were conducted including stable cell line construction, myocardial infarction modeling, imaging, Western Blot, ELISA, staining, and functional assays. Results Significant gene expression and pathway disparities were found between DLBCL and myocardial infarction samples. NOTCH1, The molecules named Recosomal-binding protein 70 (RBP-J), zeste 2 polycomb repressive complex 2 subunit (EZH2), trimethylated histone H3 at lysine 27 (H3K27me3), Signal Transducer And Activator Of Transcription 3 (STAT3) and Jumonji domain containing-3 (JMJD3) matters a lot in DLBCL. NOTCH1 inhibition decreased DLBCL cell proliferation and activity, reduced inflammatory factors, and improved myocardial fibrosis and infarction severity. NOTCH1 inhibits Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Interleukin-6 (IL-6) expressions depending on STAT3 and EZH2. Co-culturing with DLBCL cells increased fibroblast proliferation, invasion, and fibrosis. Conclusion NOTCH1 signaling influences DLBCL development and myocardial infarction severity through the EZH2/STAT3 pathway, leading to increased heart fibrosis. © 2025 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.