长链非编码RNA-PXMP4-2-4通过激活JAK2/STAT3信号通路减轻心肌细胞损伤。
Lnc-PXMP4-2-4 alleviates myocardial cell damage by activating the JAK2/STAT3 signaling pathway.
作者信息
Zhang Hong, Guo Qinlin, Feng Guiju, Shen Xin, Feng Xinxin, Guo Yi, Wang Shouyan, Zhong Xia
机构信息
Department of General Practice, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People's Republic of China.
Department of Endocrine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People's Republic of China.
出版信息
Heliyon. 2023 Jul 26;9(8):e18649. doi: 10.1016/j.heliyon.2023.e18649. eCollection 2023 Aug.
PURPOSE
The aim of this study was to investigate the protective effect of long non-coding lnc-PXMP4-2-4 on myocardial cell damage caused by acute myocardial infarction (AMI).
METHODS
Peripheral blood mononuclear cells (PBMC) were collected from 24 patients with AMI on the day of admission, the first day after percutaneous coronary intervention (PCI) and the third day after surgery, and 24 patients with clinical control group. Real-time quantitative PCR(QRT-PCR) was used to detect the expression of related genes. Then in human cardiomyocytes (AC16), Cell Counting Kit-8 (CCK-8) was used to determine cell viability, lactate dehydrogenase release assay (LDH) was used to determine the release of lactate dehydrogenase, PCR was used to detect the expression of genes, cell death was detected by flow cytometry, and the expression of related proteins was measured by Western blot. The effect of lnc-PXMP4-2-4 was further studied by silencing and overexpressing lnc-PXMP4-2-4.
RESULTS
Compared with clinical control group, the expression of lnc-PXMP4-2-4 in PBMC of AMI patients was significantly higher than it. Compared with pre-operation, the expression of lnc-PXMP4-2-4 was significantly up-regulated on day 1 after PCI, and recovered to pre-operation level on day 3 after surgery. In AC16 cells, lnc-PXMP4-2-4 inhibited the proliferation of AC16, promoted the release of LDH and increased cell death, aggravated the cardiomyocyte injury caused by HO, and inhibited the expression of JAK2 and STAT3 mRNA and protein. The up-regulation of lnc-PXMP-4-2-4 had the opposite effect. In addition, the inhibition of the signal pathway by JAK2/STAT3 pathway inhibitor AG490 partially weakened the enhanced viability of AC16 cells, decreased LDH release and apoptosis induced by lnc-PXMP4-2-4 overexpression, increased Bcl-2 expression and down-regulated Bax expression.
CONCLUSION
Therefore, we conclude that lnc-PXMP4-2-4 protects cardiomyocytes from injury by activating the JAK2/STAT3 signaling pathway.
目的
本研究旨在探讨长链非编码RNA lnc-PXMP4-2-4对急性心肌梗死（AMI）所致心肌细胞损伤的保护作用。
方法
收集24例AMI患者入院当天、经皮冠状动脉介入治疗（PCI）后第1天和术后第3天的外周血单个核细胞（PBMC），以及24例临床对照组患者的PBMC。采用实时定量聚合酶链反应（QRT-PCR）检测相关基因的表达。然后在人心肌细胞（AC16）中，使用细胞计数试剂盒-8（CCK-8）测定细胞活力，采用乳酸脱氢酶释放试验（LDH）测定乳酸脱氢酶的释放，用PCR检测基因表达，通过流式细胞术检测细胞死亡情况，并用蛋白质免疫印迹法检测相关蛋白的表达。通过沉默和过表达lnc-PXMP4-2-4进一步研究其作用效果。
结果
与临床对照组相比，AMI患者PBMC中lnc-PXMP4-2-4的表达明显高于对照组。与术前相比，PCI术后第1天lnc-PXMP4-2-4的表达明显上调，术后第3天恢复至术前水平。在AC16细胞中，lnc-PXMP4-2-4抑制AC16细胞增殖，促进LDH释放并增加细胞死亡，加重过氧化氢（HO）所致的心肌细胞损伤，并抑制JAK2和STAT3 mRNA及蛋白的表达。lnc-PXMP-4-2-4的上调则产生相反的作用。此外，JAK2/STAT3信号通路抑制剂AG490对该信号通路的抑制作用部分减弱了lnc-PXMP4-2-4过表达所增强的AC16细胞活力，降低了LDH释放及诱导的细胞凋亡，增加了Bcl-2表达并下调了Bax表达。
结论
因此，我们得出结论，lnc-PXMP4-2-4通过激活JAK2/STAT3信号通路保护心肌细胞免受损伤。
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