miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury

Díaz, Ignacio; Calderón-Sánchez, Eva; Toro, R.; Ávila-Médina, Javier; Pedro, Eva Sánchez de Rojas-de; Domínguez-Rodríguez, Alejandro; Rosado, Juan A.; Hmadcha, Abdelkrim; Ordóñez, Antonio; Smani, Tarik

doi:10.1038/s41598-017-09198-x

Cited by 52 publications

(51 citation statements)

References 55 publications

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“…Male Wistar rats weighing 250 ± 50 g were anesthetized with a mixture of O 2 /sevoflurane 2%, then with anesthesia (50 mg/kg ketamine plus 8 mg/kg xylazine i.p) as described previously ( Díaz et al, 2017 ). A small animal ventilator was used (Harvard Apparatus, Holliston, MA, United States) with a tidal volume (V t ) of 1.5–2.0 ml and 75–80 ventilations per minute.…”

Section: Methodsmentioning

confidence: 99%

“…Two microgram of RNA were retrotranscribed to cDNA with the “RT quantitec kit” (Qiagen N.V., Germany). Standard qRT-PCRs were performed as described previously ( Díaz et al, 2017 ). Data analysis was made with the “Expression Suite” software and fold change quantification was calculated using the comparative cycle threshold CT (ΔΔCT) method.…”

Section: Methodsmentioning

confidence: 99%

“…We have demonstrated recently that Ucn-1 activated the other important effector of cAMP, Epac ( Calderón-Sánchez et al, 2016 ). Epac and ERK1/2 are also involved in the Ucn-1-induced positive inotropism, in its regulation of apoptotic genes and in microRNAs expression during heart reperfusion ( Díaz et al, 2017 ). A recent study has demonstrated that sustained activation of Epac activated Ca 2+ influx through store-operated Ca 2+ entry (SOCE) via TRPC3/4 channels ( Domínguez-Rodríguez et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

et al. 2018

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Aims: Urocortin-2 (Ucn-2) is a potent cardioprotector against Ischemia and Reperfusion (I/R) injuries. However, little is known about its role in the regulation of intracellular Ca2+ concentration ([Ca2+]i) under I/R. Here, we examined whether the addition of Ucn-2 in reperfusion promotes cardioprotection focusing on ([Ca2+]i handling.Methods and Results: Cardiac Wistar rat model of I/R was induced by transient ligation of the left coronary artery and experiments were conducted 1 week after surgery in tissue and adult cardiomyocytes isolated from risk and remote zones. We observed that I/R promoted significant alteration in cardiac contractility as well as an increase in hypertrophy and fibrosis in both zones. The study of confocal [Ca2+]i imaging in adult cardiomyocytes revealed that I/R decreased the amplitude of [Ca2+]i transient and cardiomyocytes contraction in risk and remote zones. Interestingly, intravenous infusion of Ucn-2 before heart’s reperfusion recovered significantly cardiac contractility and prevented fibrosis, but it didn’t affect cardiac hypertrophy. Moreover, Ucn-2 recovered the amplitude of [Ca2+]i transient and modulated the expression of several proteins related to [Ca2+]i homeostasis, such as TRPC5 and Orai1 channels. Using Neonatal Rat Ventricular Myocytes (NRVM) we demonstrated that Ucn-2 blunted I/R-induced Store Operated Ca2+ Entry (SOCE), decreased the expression of TRPC5 and Orai1 as well as their interaction in reperfusion.Conclusion: Our study provides the first evidences demonstrating that Ucn-2 addition at the onset of reperfusion attenuates I/R-induced adverse cardiac remodeling, involving the [Ca2+]i handling and inhibiting the expression and interaction between TRPC5 and Orai1.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

et al. 2018

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“…Meanwhile microRNA-27a can suppress expression of the Apaf-1 protein to mitigate hypoxia-induced neuronal apoptosis 19 . For miR-324, miR-324-3p overexpression promoted dysregulation of genes involved in cell death and apoptosis 20 , whereas miR-212 can promote neuronal cell maturation 21 . Up-regulation of circ-camk4 would be predicted to enhance sponging of these miRNAs and in turn promote expression of genes targeted by these miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury

Zhang

Wang

et al. 2020

Sci Rep

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Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression. However, whether circRNAs have a role in cerebral I/R injury pathogenesis, especially soon after onset, is unclear. In this study, we used the SD rat middle cerebral artery occlusion (MCAO) model of stroke to examine the role of circRNAs in cerebral I/R injury. We used high-throughput sequencing (HTS) to compare the expression levels of circRNAs in cerebral cortex tissue from MCAO rats during the occlusion-reperfusion latency period 3 hours after I/R injury with those in control cerebral cortices. Our sequencing results revealed that expression levels of 44 circRNAs were significantly altered after I/R, with 16 and 28 circRNAs showing significant up-and down-regulation, respectively, relative to levels in control cortex. We extended these results in vitro in primary cultured neuron cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) using qRT-PCR to show that levels of circ-camk4 were increased in OGD/R neurons relative to control neurons. Bioinformatics analyses predicted that several miRNAs could be associated with circ-camk4 and this prediction was confirmed in a RNA pull-down assay. KEGG analysis to predict pathways that involve circ-camk4 included the glutamatergic synapse pathway, MAPK signaling pathway, and apoptosis signaling pathways, all of which are known to be involved in brain injury after I/R. Our results also demonstrate that levels of the human homolog to circ-camk4 (hsa-circ-camk4) are elevated in SH-SY5Y cells exposed to OGD/R treatment. Overexpression of hsa-circ-camk4 in SH-SY5Y cells significantly increased the rate of cell death after OGD/R, suggesting that circ-camk4 may play a key role in progression of cerebral I/R injury.

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“…Wu et al showed that hypoxia/ reoxygenation significantly increased the release of lactate dehydrogenase, levels of malondialdehyde, and cardiomyocyte apoptosis, but these effects were attenuated by an miR-613 mimic, and programmed cell death 10 (PDCD10) was identified as a target gene of miR-613, suggesting that miR-613 inhibits I/R-induced cardiomyocyte apoptosis by targeting PDCD10 [28]. Díaz et al indicated that administration of urocortin-1 and urocortin-2 at the beginning of reperfusion significantly restored cardiac function, and intravenous infusion of urocortin-2 in rat model of I/R mimicked the effect of urocortin-1 on miR-324-3p and miR-139-3p, suggesting that a role of urocortin in myocardial protection may be involved in posttranscriptional regulation with miRNAs [29]. In this study, we unveiled differential expression of many mRNAs and lncRNAs in the myocardial ischemic regions, further suggesting that these altered genes might be involved in the response to cardiac injury.…”

Section: Discussionmentioning

confidence: 99%

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

Li¹,

Lin²,

He³

et al. 2018

Oncotarget

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We used Agilent Gene Expression microarray to analyze differential gene and lncRNA expression patterns in the myocardial ischemia regions during ischemia/ reperfusion (I/R)-induced cardiac injury in rats. Male SD rats were assigned into control group, 2 h group (30 min ischemia followed by 2 h reperfusion), 0.5 h (30 min ischemia followed by 0.5h reperfusion) group. We observed that of 18090 lncRNAs, an average of 233 lncRNAs was up-regulated in ischemic tissues of 2 h group, compared with those in control group, while an average of 6115 lncRNAs was down-regulated (with a > 2.0 fold-change and p < 0.05). Further, a total of 3135 mRNAs were differentially expressed between control group and 2h group, in which 542 mRNAs were up-regulated and 2593 mRNAs were down-regulated. Some differentially expressed genes were validated by qRT-PCR analyses of select lncRNAs in different time points after cardiac I/R injury. We unveiled that the expressions of lncRNA XR_345533.2, NONRATT025386, NONRATT024318, XR_599241.1, and NONRATT025509 were significantly up-regulated in 2h group compared with control group and 0.5h group, whereas the expression of lncRNA NR_130708.1 was downregulated after cardiac I/R injury and had no statistically different between 0.5h group and 2h group. Otherwise, the expressions of lncRNA NONRATT028627, NONRATT021959, XR_590005.1 and NONRATT023191 were significantly up-regulated in 2h group compared with 0.5h group. These findings provide evidence for differential expression patterns of mRNAs and lncRNAs in the ischemic tissues after cardiac I/R injury in rats.

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miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury

Cited by 52 publications

References 55 publications

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

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