RNA sequencing revealing the role of AMP-activated protein kinase signaling in mice myocardial ischemia reperfusion injury

Sun, Huankun; Wang, Jiaoni; Que, Jia-Qun; Peng, Yu; Yu, Yong-Wei; Wang, Lei; Ye, Haihao; Huang, Kaiyu; Xue, Yan; Zhou, Yingying; Ji, Kangting

doi:10.1016/j.gene.2019.04.010

Cited by 11 publications

(10 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In reference to previous studies, LncGAS5 is upregulated in MIRI model [13]. In this work, it was further confirmed, and later, through adenovirus injection, silenced LncGAS5 expression was present in MIRI model mice (Figure 2a).…”

Section: Lncgas5 Is Up-regulated In Miri; Silencing Lncgas5 Inhibits Mirisupporting

confidence: 88%

“…Long noncoding RNA growth arrest specific transcript 5 (lncGAS5) is important for LncRNA family, and it has been found to act pivotally in regulating cancer, rhinitis, and systemic lupus erythematosus [10][11][12]. Recent studies have found that lncGAS5 is differentially expressed in MIRI models, and that lncGAS5 has a promoting impact on MIRI cardiomyocyte apoptosis [13,14]. But the underlying molecular mechanism of lncGAS5 affecting MIRI has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long non-coding RNA growth arrest specific transcript 5 acting as a sponge of MicroRNA-188-5p to regulate SMAD family member 2 expression promotes myocardial ischemia-reperfusion injury

Dong

Bai

et al. 2021

Bioengineered

View full text Add to dashboard Cite

The purpose of this work is to probe into the potential role of long non-coding RNA growth arrest specific transcript 5 (lncGAS5)/ microRNA (miR)-188-5p/SMAD2 axis in MIRI. Through ligating the left anterior descending (LAD) coronary artery, MIRI animal model and hypoxia/reoxygenation (H/R) myocardial injury model in vitro were established. Via adenovirus or plasmid transfection, lncGAS5/ MiR-188-5p/SMAD2 expression was up-regulated or down-regulated in the study. RT-qPCR was applied to check LncGAS5/MiR-188-5p/SMAD2 mRNA expression, HE staining for histopathological staining, TUNEL staining and flow cytometry to examine cardiomyocyte apoptotic rate, CCK-8 to check cell viability, ELISA to detect inflammatory factor levels, Western blot to examine Bax, Bcl-2, cleaved caspase-3, NF-κB and SMAD2 expression, and dual luciferase reporter experiment to examine the targeting relationship of miR-188-5p with LncGAS5 and SMAD2. The results indicated that LncGAS5 and SMAD2 were highly expressed in MIRI and miR-188-5p was under-expressed. Silencing LncGAS5 and SMAD2 or overexpressing miR-188-5p could reduce MIRI in myocardial tissue, cardiomyocyte apoptosis, inhibit Bax, cleaved caspase-3 and NF-κB expressions and promote Bcl-2 expression, while reducing inflammatory factors TNF -α, IL-1β and IL-6 levels. Overexpressing LncGAS5 promoted MIRI. Additionally, the impact of silencing LncGAS5 on MIRI could be reversed through inhibiting miR-188-5p. LncGAS5 acted as a sponge of miR-188-5p to target SMAD2 expression. In conclusion, Silencing LncGAS5 is available to improve MIRI through regulating miR-188-5p/SMAD2 axis, and may be used as a potential target for treating MIRI in the future.

show abstract

Section: Lncgas5 Is Up-regulated In Miri; Silencing Lncgas5 Inhibits Mirisupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA growth arrest specific transcript 5 acting as a sponge of MicroRNA-188-5p to regulate SMAD family member 2 expression promotes myocardial ischemia-reperfusion injury

Dong

Bai

et al. 2021

Bioengineered

View full text Add to dashboard Cite

show abstract

“…Previous literature reported that ATG4C expression was down-regulated in myocardial tissue of mice with myocardial I/R damage [ 27 ], which implied that ATG4C might be a potential regulator involving in the cardiomyocyte’s functions. Herein, the influence of H/R stimulation and EGCG treatment on ATG4C expression in H9c2 cells was tested.…”

Section: Resultsmentioning

confidence: 99%

Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression

et al. 2021

View full text Add to dashboard Cite

Myocardial ischemia/reperfusion (I/R) injury is a serious issue during the therapy of myocardial infarction. Herein, we explored the beneficial influence of Epigallocatechin-3-gallate (EGCG) on hypoxia/reoxygenation (H/R)-stimulated cardiomyocyte H9c2 cells damage, along with possible internal molecular mechanism related autophagy related 4C (ATG4C). H9c2 cells were subjected to H/R stimulation and/or EGCG treatment. ATG4C mRNA expression was measured via q-PCR assay. ATG4C overexpression plasmid (OE-ATG4C) was transfected to arise ATG4C level. Cell viability, apoptosis, reactive oxygen species (ROS) production, ATP level were tested via CCK-8 assay, Annexin V-FITC/PI staining, DCFH-DA staining and ATP Assay Kit, respectively. Western blotting was performed to test Cleaved-caspase 3, Cleaved-caspase 9, cytochrome C, and LC3B protein levels. H/R stimulation resulted in H9c2 cell viability loss, promoted cell apoptosis, and ROS overproduction, as well as lowered ATP level in cells. EGCG treatment alleviated H/R-resulted H9c2 cell viability loss, cell apoptosis, ROS overproduction, and reduction of ATP level. Moreover, H/R stimulation reduced the ATG4C expression in H9c2 cells, while EGCG raised the ATG4C expression. Overexpression of ATG4C strengthened the beneficial influence of EGCG on H/R-stimulated H9c2 cell viability, apoptosis and ROS production. Besides, ATG4C overexpression weakened the H/R-stimulated H9c2 cell autophagy via reducing LC3B II/I expression. EGCG exerted beneficial influence on H/R-stimulated cardiomyocytes, which protected cardiomyocytes from H/R-stimulated viability loss, apoptosis, and ROS overproduction via enhancing ATG4C expression.

show abstract

“…The threshold used to screen RNAs with |log 2 FC| >1 was P<0.05. |log 2 FC| >1 is to screen genes with multiples of difference >2 times (34,35). Gene Ontology (GO) analysis (http://www.geneontology.org) described the molecular function, cellular component and biological process of differentially expressed transcripts.…”

Section: Methodsmentioning

confidence: 99%

Characterization of novel lncRNAs in upper thoracic spinal cords of rats with myocardial ischemia‑reperfusion injuries

Wang

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

Myocardial ischemia-reperfusion injury (MIRI) is a significant problem in clinical cardiology, and refers to a more serious myocardial injury caused by blood recanalization after a period of myocardial ischemia, as compared with injury caused by vascular occlusion. The spinal cord, as the primary afferent and efferent center of cardiac sensory and sympathetic nerve fibres, has received increased attention in recent years with regards to the regulation of MIRIs. Previous studies have revealed that MIRI has a strong correlation with the abnormal expression of long non-coding (lnc)RNAs in the myocardium; however, there are limited reports on the effects of the altered expression of lncRNAs in the spinal cord following MIRI. To investigate the expression patterns of lncRNAs in the spinal cord after MIRI and their potential role in the early stage of reperfusion, a MIRI model was established in rats. After 30 min of myocardial ischemia and 2 h of reperfusion, the upper thoracic spinal cord tissues were immediately dissected and isolated. lncRNAs and mRNAs in spinal cord tissues were screened using transcriptome sequencing technology, and the expression of several highly deregulated mRNAs, including Frs3, Zfp52, Dnajc6, Nedd4l, Tep1, Myef2, Tgfbr1, Fgf12, Mef2c, Tfdp1 and lncRNA, including ENSRNOT00000080713, ENSRNOT00000090564, ENSRNOT00000082588, ENSRNOT00000091080, ENSRNOT00000091570, ENSRNOT00000087777, ENSRNOT00000082061, ENSRNOT00000091108, ENSRNOT00000087028, ENSRNOT00000086475, were further validated via reverse transcription-quantitative PCR. The number of altered expressed lncRNAs was 126, among which there were 41 upregulated probe sets and 85 downregulated sets. A total of 470 mRNAs were differentially expressed, in which 231 probe sets were upregulated and 239 were downregulated. Gene Ontology analysis indicated that dysregulated transcripts related to biological processes were mainly associated with ‘cell-cell signaling’. Moreover, pathway analysis demonstrated significant changes in the ‘PI3K/Akt signaling pathway’ and the ‘p53 signaling pathway’. Thus, the altered expression of lncRNAs in the spinal cord may be of considerable importance in the process of MIRI. The present results could provide an insight into the potential roles and mechanism of lncRNAs during the early stage of reperfusion.

show abstract

RNA sequencing revealing the role of AMP-activated protein kinase signaling in mice myocardial ischemia reperfusion injury

Cited by 11 publications

References 30 publications

Long non-coding RNA growth arrest specific transcript 5 acting as a sponge of MicroRNA-188-5p to regulate SMAD family member 2 expression promotes myocardial ischemia-reperfusion injury

Long non-coding RNA growth arrest specific transcript 5 acting as a sponge of MicroRNA-188-5p to regulate SMAD family member 2 expression promotes myocardial ischemia-reperfusion injury

Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression

Characterization of novel lncRNAs in upper thoracic spinal cords of rats with myocardial ischemia‑reperfusion injuries

Contact Info

Product

Resources

About