1. Academic Validation
  2. Exosomes Released from CaSR-Stimulated PMNs Reduce Ischaemia/Reperfusion Injury

Exosomes Released from CaSR-Stimulated PMNs Reduce Ischaemia/Reperfusion Injury

  • Oxid Med Cell Longev. 2021 Jan 12;2021:3010548. doi: 10.1155/2021/3010548.
Tai-Yu Zhai 1 Bao-Hong Cui 1 Yang Zhou 1 Xin-Yu Xu 1 Lei Zou 1 Xin Lin 1 Xiao-Shuang Zhu 1 Si-Wen Zhang 1 Wan-Lin Xie 1 Yang-Yang Cheng 1 Yi-Hua Sun 1
Affiliations

Affiliation

  • 1 Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin 150086, China.
Abstract

Ischemia-reperfusion (I/R) injury caused by acute myocardial infarction (AMI) can initiate a strong inflammatory response. Polymorphonuclear cells (PMNs) are the most important inflammatory cells. Our previous studies found that the calcium-sensing receptor (CaSR) regulates the proinflammatory effects of PMNs. However, the role and mechanism of CaSR-regulated PMNs in I/R injury remain uncertain. A rat AMI model was developed in this study and showed that the expression of CaSR on PMNs increased in AMI; however, the levels of Bcl-xL and SOD in myocardial tissue decreased, while Bax and MDA levels increased. Then, after coculture with CaSR-stimulated PMNs, the expression of Bcl-xL in cardiomyocytes significantly increased, Bax expression and the apoptotic rate decreased, and ROS production was significantly inhibited. At the same time, the cardiomyocyte damage caused by hypoxia-reoxygenation was reduced. Furthermore, we found that exosomes derived from PMNs could be taken up by cardiomyocytes. Additionally, the exosomes secreted by CaSR-stimulated PMNs had the same effect on cardiomyocytes as CaSR-stimulated PMNs, while the increased phosphorylation level of Akt in cardiomyocytes could be revered by Akt transduction pathway inhibitors. Subsequently, we identified the exosomes derived from CaSR-stimulated PMNs by second-generation Sequencing technology, and increased expression of lncRNA ENSRNOT00000039868 was noted. The data show that this lncRNA can prevent the hypoxia-reoxygenation injury by upregulating the expression of PDGFD in cardiomyocytes. In vivo, exosomes from CaSR-stimulated PMNs played a significant role against AMI and reperfusion injury in myocardial tissue. Thus, we propose that exosomes derived from CaSR-stimulated PMNs can reduce I/R injury in AMI, and this effect may be related to the Akt signaling pathway.

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