Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, PR China.
Department of Cardiovascular Surgery, NanFang hospital, Southern Medical University, GuangZhou 515000, Guangdong Province, PR China.
Life Sci. 2023 Aug 1;326:121805. doi: 10.1016/j.lfs.2023.121805. Epub 2023 May 24.
P2Y14 receptor is expressed in neutrophils and is involved in activation of inflammatory signaling. However, the expression and function of P2Y14 receptor in neutrophils after myocardial infarction/reperfusion (MIR) injury remain to be elucidated.
In this research, rodent and cellular models of MIR were used to detect the involvement and function of P2Y14 receptor, as well as the regulation of inflammatory signaling via P2Y14 receptor in neutrophils post-MIR.
In the early stage post MIR, the expression of P2Y14 receptor was upregulated in CD4Ly-6G neutrophils. Additionally, the expression of P2Y14 receptor was highly induced in neutrophils subjected to uridine 5'-diphosphoglucose (UDP-Glu), which is proven to be secreted by cardiomyocytes during ischemia and reperfusion. Our results also showed the beneficial role of P2Y14 receptor antagonist PPTN in counteracting inflammation via promoting polarization of neutrophils to N2 phenotype in the infarct area of the heart tissue after MIR.
These findings prove that the P2Y14 receptor is involved in the regulation of inflammation in the infarct area after MIR, and establish a novel signaling pathway concerning the interplay between cardiomyocytes and neutrophils in the heart tissue.
P2Y14 受体在中性粒细胞中表达，并参与炎症信号的激活。然而，心肌梗死/再灌注（MIR）损伤后中性粒细胞中 P2Y14 受体的表达和功能仍有待阐明。
本研究使用鼠和细胞模型来检测 P2Y14 受体在 MIR 后中性粒细胞中的参与和功能，以及 P2Y14 受体对中性粒细胞中炎症信号的调节。
在 MIR 后早期，CD4Ly-6G 中性粒细胞中 P2Y14 受体的表达上调。此外，在 UTP-Glu 处理的中性粒细胞中，P2Y14 受体的表达被高度诱导，UTP-Glu 被证明是在缺血和再灌注期间由心肌细胞分泌的。我们的结果还表明，P2Y14 受体拮抗剂 PPTN 在 MIR 后心脏组织梗死区通过促进中性粒细胞向 N2 表型极化来对抗炎症的有益作用。
这些发现证明了 P2Y14 受体参与了 MIR 后梗死区炎症的调节，并建立了一条涉及心肌细胞和中性粒细胞在心脏组织中相互作用的新信号通路。
