ERG mediates the inhibition of NK cell cytotoxicity through the HLX/STAT4/Perforin signaling pathway, thereby promoting the progression of myocardial infarction
- PMID:38091230
- DOI: 10.1007/s13105-023-00999-5
ERG mediates the inhibition of NK cell cytotoxicity through the HLX/STAT4/Perforin signaling pathway, thereby promoting the progression of myocardial infarction
Abstract
This study aimed to investigate the role of ERG in the HLX/STAT4/Perforin signaling axis, impacting natural killer (NK) cell cytotoxicity and myocardial infarction (MI) progression. NK cell cytotoxicity was assessed via co-culture and 51Cr release assays. Datasets GSE34198 and GSE97320 identified common differentially expressed genes in MI. NK cell gene expression was analyzed in MI patients and healthy individuals using qRT-PCR and Western blotting. ERG's regulation of HLX and STAT4's regulation of perforin were studied through computational tools (MEM) and ChIP experiments. HLX's influence on STAT4 was explored with the MG132 proteasome inhibitor. Findings were validated in a mouse MI model.ERG, a commonly upregulated gene, was identified in NK cells from MI patients and mice. ERG upregulated HLX, leading to STAT4 proteasomal degradation and reduced Perforin expression. Consequently, NK cell cytotoxicity decreased, promoting MI progression. ERG mediates the HLX/STAT4/Perforin axis to inhibit NK cell cytotoxicity, fostering MI progression. These results provide vital insights into MI's molecular mechanisms.
Keywords: ERG; HLX; Molecular mechanisms; Mouse model; Myocardial infarction; NK cells; Perforin; STAT4.
© 2023. The Author(s) under exclusive licence to University of Navarra.
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