Research Paper Volume 15, Issue 18 pp 9877—9889
Myeloid-specific knockout of SHP2 regulates PI3K/PLCγ signaling pathway to protect against early myocardial infarction injury
- 1 Department of Cardiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- 2 Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
Received: April 24, 2023 Accepted: August 29, 2023 Published: September 26, 2023
https://doi.org/10.18632/aging.205096How to Cite
Copyright: © 2023 Sha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objectives: To study the effects of myeloid-specific knockout of SHP2 on early myocardial infarction and explore its molecular mechanism.
Methods: The model of myocardial infarction was established by using SHP2 in myeloid-specific knockout mice, and the effect of SHP2MAC-KO on myocardial function was detected by echocardiography. The effects of SHP2 on myocardial infarct size in myeloid-specific knockout mice was examined by TTC assay and Masson staining. Then, the detection of apoptosis was performed using TUNEL staining and inflammatory cell infiltration was observed using immunohistochemical staining. Moreover, macrophages in mouse hearts were selected by Flow Cytometry and treated with PI3K inhibitors respectively. Western blotting was then used to detect protein expression of p-SHP2 and PI3K/PLCγ signaling pathway. The phagocytic ability of cells was detected by endocytosis test, and the expression of inflammatory cytokines was detected by ELISA.
Results: Specific knockout of SHP2 in mice with myocardial infarction can improve the cardiac function, decrease infarct size, and reduce apoptosis as well as inflammatory cell infiltration. It also can mediate the PI3K/PLCγ signaling pathway in macrophages, which in turn enhances the endocytosis of macrophages and reduces the expression of inflammatory cytokines in macrophages.
Conclusions: Myeloid-specific knockout of SHP2 regulates PI3K/PLCγ signaling pathway to protect against early myocardial infarction injury.