Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure

Zhu, Haijuan; Han, Zhengyi; He, Songqing; Jin, Shiyun; Xu, Shijie; Fang, Xiangdong; Zhang, Ye

doi:10.1016/j.lfs.2016.11.028

Cited by 15 publications

(7 citation statements)

References 42 publications

(34 reference statements)

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“…Thus, it is reasonable to speculate that HPC induced cardioprotection was mediated by the upregulation of miR-133b-5p. The finding is in agreement with the previous observation on a cardiac protective role of miRNAs ( 34 ). Yin et al ( 35 ) reported that an ischemic stimulus induced the expression of miR-1, miR-21 and miR-24, and injection of these IPC-derived miRNAs directly into the left ventricle reduced myocardial IS, indicating that preconditioning induced miRNAs produced a protective phenotype following ischemic injury.…”

Section: Discussionsupporting

confidence: 93%

miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes

Pan

Han

et al. 2018

Mol Med Report

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In a previous study using a microRNA (miRNA/miR) microarray assay, we demonstrated that miR-133b-5p was upregulated in response to hypoxic preconditioning (HPC). The present study was designed to investigate the role of the miR-133b-5p in HPC-induced cardioprotection and the underlying mechanisms involving caspase-8 and caspase-3 apoptotic signaling. Adult rats were subjected to myocardial ischemia/reperfusion (I/R) injury with or without ischemic preconditioning (IPC), and the level of miR-133b-5p in myocardium was measured. Neonatal rat cardiomyocytes were isolated and subjected to hypoxia/reoxygenation (H/R) injury, with or without HPC. miR-133b-5p antagomir was transfected into the cardiomyocytes to observe whether it could block HPC-induced cardioprotection. Cellular injury was evaluated by detecting cell viability, lactate dehydrogenase (LDH) activity and apoptotic rate. Reverse transcription-quantitative polymerase chain reaction was used to measure the level of miR-133b-5p. The activation of caspase-8 and caspase-3 were measured by western blot analysis to detect the cleaved fragments as well as a colorimetric assay. Following myocardial I/R injury, the expression of miR-133b-5p was decreased in myocardium, while this decrease was restored by IPC. HPC protected neonatal rat cardiomyocytes against H/R injury by increasing cell viability, while reducing LDH release and cell apoptosis. These protective effects were coupled with the upregulation of miR-133b-5p. However, the knockdown of miR-133b-5p in the cardiomyocytes blocked HPC-mediated cardioprotection as reflected by the aggravation of cell injury and apoptosis. HPC upregulated miR-133b-5p level was markedly suppressed by the antagomir. In addition, the cleavage and activities of caspase-8 and caspase-3 were inhibited by HPC while reversed by knockdown of miR-133b-5p. Upregulation of miR-133b-5p contributes to HPC-mediated cardioprotection in cardiomyocytes, and the mechanism may be associated with inhibition of caspase-8 and caspase-3 apoptotic signaling.

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Section: Discussionsupporting

confidence: 93%

miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes

Pan

Han

et al. 2018

Mol Med Report

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“…In the present study, miR‐181a‐1 levels were decreased with I/R injury but increased significantly with PostC. Similarly, it was demonstrated that miR‐181a‐5p levels were decreased in chronic heart failure following doxorubicin administration in a cardiomyocyte culture 49 . Besides this, miR‐181a levels were decreased with I/R simulation in newborn cardiomyocyte cultures, and this effect was inhibited by PostC 30 .…”

Section: Discussionsupporting

confidence: 78%

“…Similarly, it was demonstrated that miR-181a-5p levels were decreased in chronic heart failure following doxorubicin administration in a cardiomyocyte culture. 49 Besides this, miR-181a levels were decreased with I/R simulation in newborn cardiomyocyte cultures, and this effect was inhibited by PostC. 30 In a study carried out in rats, miR-181a was downregulated immediately after retinal I/R, and the levels were found to have decreased further at 24 and 72 hours post-injury.…”

Section: Apoptosis Is Regarded As a Vital Component In Various Procesmentioning

confidence: 96%

The inhibition of apoptosis through myocardial postconditioning by affecting Fas/FasIg signaling through miR139‐3p and miR181a‐1

2020

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Background and Aim of the study Ischemic postconditioning (PostC) is considered to be one of the strongest mechanisms limiting the extent of myocardial infarction, and reducing ischemia‐reperfusion (I/R) injury. I/R‐induced myocardial injury results in apoptosis, autophagy, and necrosis. The aim of the present study was to investigate the roles of the necrotic gene cytochrome b‐245 beta chain (Cybb); Cybb‐related microRNA miR139‐3p; the autophagy gene Beclin‐1 (Becn1); proapoptotic genes Fas, Faslg and growth arrest and DNA‐damage‐inducible 45 alpha (Gadd45a); and apoptosis‐related microRNA miR181a‐1 levels on I/R injury, as well as, the potential protective effects of PostC through this gene and microRNAs. Methods The left main coronary artery was subjected to ischemia for 30 minutes, followed by reperfusion for 120 minutes. PostC involved three cycles of I/R, each lasting 10 seconds. Gene and microRNA levels were analyzed using a quantitative reverse transcription‐polymerase chain reaction. Results Although an increase was observed in the expression levels of the Cybb, Fas, Faslg and Gadd45a genes, the miR139‐3p, miR181a‐1, and Becn1 expression levels were found to decrease with I/R injury. PostC was determined to restore the expression of all the genes to the normal levels. Conclusions The abovementioned genes can be used as important prognostic markers in the diagnosis of reperfusion injury and in the evaluation of treatment efficacy. It was further noted that increased expression of CYBB, which is one of the target genes for miR139‐3p, and a decreased expression of miR181a‐1 may cause apoptosis by affecting Fas and Faslg signaling. PostC can inhibit apoptosis by increasing miR139‐3p and miR181a‐1 levels.

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“…All samples were carefully selected for full term singleton pregnancies, non-complicated by maternal health conditions such as infection, which was necessary in reducing inter-sample variability. We observed that most of the up-regulated miRs regulated genes relevant to hypoxia responses [35–39], vascular disease [40–44], metabolism [45–49], inflammation [50–51], or were previously reported in pre-eclamptic placentas [52–55]. In contrast, the down-regulated miRs were for the most part relevant for genes with a role in obesity or cancers [56–58], though several had also been reported in association with pregnancy disorders involving placental insufficiency [52, 55,59–61].…”

Section: Resultsmentioning

confidence: 99%

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport

et al. 2017

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Placental insufficiency leading to intrauterine growth restriction (IUGR) demonstrates perturbed gene expression affecting placental angiogenesis and nutrient transfer from mother to fetus. To understand the post-transcriptional mechanisms underlying such placental gene expression changes, our objective was to identify key non-coding microRNAs that express biological function. To this end, we initially undertook microarrays targeting microRNAs in a small sub-set of placentas of appropriate (AGA) versus small for gestational age (SGA) weight infants, and observed up-regulation of 97 miRs and down-regulation of 44 miRs in SGA versus AGA. In a larger cohort of samples (AGA, n = 21; SGA, n = 11; IUGR subset, n = 5), we validated by qRT-PCR differential expression of three specific microRNAs (miR-10b, -363 and -149) that target genes mediating angiogenesis and nutrient transfer. Validation yielded an increase in miR-10b and -363 expression of ~2.5-fold (p<0.02 each) in SGA versus AGA, and of ~3-fold (p<0.005) in IUGR versus AGA, with no significant change despite a trending increase in miR-149. To further establish a cause-and-effect paradigm, employing human HTR8 trophoblast cells, we assessed the effect of nutrient deprivation on miR expression and inhibition of endogenous miRs on target gene expression. In-vitro nutrient deprivation (~50%) increased the expression of miR-10b and miR-149 by 1.5-fold (p<0.02) while decreasing miR-363 (p<0.0001). Inhibition of endogenous miRs employing antisense sequences against miR-10b, -363 and -149 revealed an increase respectively in the expression of the target genes KLF-4 (transcription factor which regulates angiogenesis), SNAT1 and 2 (sodium coupled neutral amino acid transporters) and LAT2 (leucine amino acid transporter), which translated into a similar change in the corresponding proteins. Finally to establish functional significance we performed dual-luciferase reporter assays with 3’-insertion of miR-10b alone and observed a ~10% reduction in the 5’-luciferase activity versus the control. Lastly, we further validated by microarray and employing MirWalk software that the pathways and target genes identified by differentially expressed miRs in SGA/IUGR compared to AGA are consistent in a larger cohort. We have established the biological significance of various miRs that target common transcripts mediating pathways of importance, which are perturbed in the human IUGR placenta.

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Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure

Cited by 15 publications

References 42 publications

miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes

miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes

The inhibition of apoptosis through myocardial postconditioning by affecting Fas/FasIg signaling through miR139‐3p and miR181a‐1

Differential microRNA expression in human placentas of term intra-uterine growth restriction that regulates target genes mediating angiogenesis and amino acid transport

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