2. Academic Validation
  3. Upregulation of P2Y14 receptor in neutrophils promotes inflammation after myocardial ischemia/reperfusion injury

Upregulation of P2Y14 receptor in neutrophils promotes inflammation after myocardial ischemia/reperfusion injury

  • Life Sci. 2023 Aug 1:326:121805. doi: 10.1016/j.lfs.2023.121805.
Kunsheng Li 1,  Pengyu Zhou 2,  Jie Li 1,  Yongqing Cheng 1,  Shiliang Li 3,  Yumeng Wang 1,  Weipeng Jiang 4,  Yang Bai 3,  Hailong Cao 1,  Dongjin Wang 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Cardiovascular Surgery, NanFang hospital, Southern Medical University, GuangZhou 515000, Guangdong Province, PR China.
  • 3 Department of Cardiac Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, PR China.
  • 4 Department of Cardiology, South China Hospital of Shenzhen University, Longgang District, Shenzhen 518111, PR China.
  • 5 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. Electronic address: dongjin_wang@sina.com.
PMID: 37236604 DOI: 10.1016/j.lfs.2023.121805
Abstract

Background: 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.

Methods: 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.

Results: In the early stage post MIR, the expression of P2Y14 Receptor was upregulated in CD4+Ly-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.

Conclusion: 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.

Keywords

Inflammation; Myocardial ischemia/reperfusion; Neutrophil; P2Y14 receptor; UDP-glucose.

Figures
Products