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Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling

  • Authors:
    • Yazhong Liu
    • Hongshan Yin
    • Tao Wang
    • Tao Chen
    • Chengda Guo
    • Fue Zhang
    • Zhian Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Disease and Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 155
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    Published online on: April 8, 2025
       https://doi.org/10.3892/mmr.2025.13520
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Abstract

The objective of the present study was to investigate the impact of myeloid Src homology region 2‑containing protein tyrosine phosphatase 2 (SHP2) on myocardial ischemia reperfusion (MI/R) injury and the underlying mechanism. Bioinformatics was used to analyze genes specifically associated with MI/R. In addition, myeloid‑specific SHP2 knockout mice and wild‑type mice were subjected to MI/R or sham surgery. Echocardiography and Masson's staining were used to observe the myocardial function and infarct area of the mice. In addition, double immunofluorescence staining was used to detect the relative fluorescence intensity of SHP2 and bromodomain‑containing protein 4 (BRD4) in bone marrow‑derived macrophages (BMMs) from the mice. Western blot analysis was conducted to determine the expression levels of SHP2, BRD4, spleen tyrosine kinase (SYK), stimulator of interferon genes (STING), NADPH oxidase 4 (NOX4), NLR family pyrin domain containing 3 (NLRP3), IL‑1β and gasdermin D (GSDMD) in BMMs and mouse myocardial cells co‑cultured with the BMMs. In addition, flow cytometry was employed to assess myocardial cell apoptosis. Bioinformatics analysis revealed the downregulated expression of SHP2 and upregulated expression of BRD4 and SYK in mice with MI/R. The deletion of myeloid SHP2 aggravated MI/R injury, impaired cardiac function and increased the infarct area in mice. In addition, myeloid SHP2 deletion in BMMs promoted the expression of BRD4, SYK, STING, NOX4 and NLRP3 in BMMs, and the expression of IL‑1β and GSDMD in mouse myocardial cells co‑cultured with the BMMs. In addition, the deletion of myeloid SHP2 promoted cardiomyocyte apoptosis. These results indicate that myeloid SHP2 inhibits MI/R injury by regulating BRD4/SYK/STING/NOX4/NLRP3 signaling in BMMs.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Yin H, Wang T, Chen T, Guo C, Zhang F and Jiang Z: Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling. Mol Med Rep 31: 155, 2025.
APA
Liu, Y., Yin, H., Wang, T., Chen, T., Guo, C., Zhang, F., & Jiang, Z. (2025). Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling. Molecular Medicine Reports, 31, 155. https://doi.org/10.3892/mmr.2025.13520
MLA
Liu, Y., Yin, H., Wang, T., Chen, T., Guo, C., Zhang, F., Jiang, Z."Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling". Molecular Medicine Reports 31.6 (2025): 155.
Chicago
Liu, Y., Yin, H., Wang, T., Chen, T., Guo, C., Zhang, F., Jiang, Z."Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling". Molecular Medicine Reports 31, no. 6 (2025): 155. https://doi.org/10.3892/mmr.2025.13520
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Yin H, Wang T, Chen T, Guo C, Zhang F and Jiang Z: Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling. Mol Med Rep 31: 155, 2025.
APA
Liu, Y., Yin, H., Wang, T., Chen, T., Guo, C., Zhang, F., & Jiang, Z. (2025). Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling. Molecular Medicine Reports, 31, 155. https://doi.org/10.3892/mmr.2025.13520
MLA
Liu, Y., Yin, H., Wang, T., Chen, T., Guo, C., Zhang, F., Jiang, Z."Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling". Molecular Medicine Reports 31.6 (2025): 155.
Chicago
Liu, Y., Yin, H., Wang, T., Chen, T., Guo, C., Zhang, F., Jiang, Z."Myeloid SHP2 attenuates myocardial ischemia‑reperfusion injury via regulation of BRD4/SYK/STING/NOX4/NLRP3 signaling". Molecular Medicine Reports 31, no. 6 (2025): 155. https://doi.org/10.3892/mmr.2025.13520
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