δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

Zhi, Feng; Li, Xue; Shao, Ningsheng; Deng, Danni; Kang, Xiaoming; Chao, Dongman; Xu, Yuan; Wang, Rong; Yang, Yilin; Xia, Ying

doi:10.1159/000447815

Cited by 25 publications

(24 citation statements)

References 52 publications

(48 reference statements)

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“…We monitored hypoxia-induced changes in the liver and body weights and investigated 20 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-30e-5p, miR-34a-5p, miR-34c-5p, miR-107-3p, miR-122-5p, miR-125a-5p, miR-128a-3p, miR-135b-5p, miR-142-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-182, miR-184, miR-192-5p, and miR-204-5p) that differentially respond to hypoxic stress based on our microarray and PCR analyses of miRNAs in the hypoxic kidney [26], cortex [25], and heart [27]. …”

Section: Resultsmentioning

confidence: 99%

“…Chronic hypoxia was induced as described in our previous work [25-27]; the O 2 level was maintained at 9.5%–10% in the plexiglass box to induce hypoxia. The rats of Groups C and D were kept in the hypoxic box for 1, 5, or 10 days.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, we found the involvement of DOR in the regulation of miRNA expression in the brain, kidney and heart [25-27]. All the brain, heart and kidney are hypoxia/ischemia sensitive organs.…”

Section: Introductionmentioning

confidence: 99%

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Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O₂) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected according to TaqMan low-density array (TLDA) data and analyzed by quantitative real-time PCR. Results: We found that: 1) 1-day hypoxia caused the upregulation of 9 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-122-5p, miR-128a-3p, miR-135b-5p, miR-145-5p, and miR-181a-5p) and the downregulation of 2 miRNAs (miR-34a-5p and miR-182); 2) 5 and 10-days hypoxia altered the expression of 4 miRNAs (miR-34c-5p, miR-184, miR-107-3p and miR192-5p); 3) DOR activation shifted the expression of 8 miRNAs (miR-122-5p, miR-146a-5p, miR-30e-5p, miR-128a-3p, miR-182, miR-192-5p miR-107-3p and miR-184) in normoxic condition; and 4) DOR activation modified hypoxia-induced changes in 6 miRNAs (miR-142-5p, miR-145-5p, miR-146a-5p, miR-204-5p, miR-34a-5p and miR-192-5p). Conclusion: Hypoxia significantly modifies the miRNA profile in the liver, while DOR activation can modify the hypoxic modification. Therefore, it is potentially possible to alter hypoxic/ischemic pathophysiology in the liver through DOR pharmacotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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“…It has been demonstrated that several miRs are associated with cardioprotection of ischemic postconditioning following myocardial ischemia/reperfusion, such as miR-29b, -133a, and -146b [11]. Hypoxia significantly modifies the miRNA profile in the heart [12]. Notable research has also demonstrated that autophagy takes part in the occurrence and development of almost all cardiovascular diseases [13-15].…”

Section: Introductionmentioning

confidence: 99%

Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Coronary microembolization (CME) can lead to no-reflow or slow reflow, which is one of the important reasons for loss of clinical benefit from myocardial reperfusion therapy. MicroRNAs and autophagy are heavily implicated in the occurrence and development of almost all cardiovascular diseases. Therefore, the present study was designed to investigate the role of miR-30e-3p and autophagy in CME-induced myocardial injury rat model. Methods: Sixty rats were randomly divided into six groups: sham, CME 1h,3h,6h,9h, and 12h (n = 10 per group). Our CME rat model was created by injecting polyethylene microspheres (42mm) into the left ventricle of the heart; the sham group was injected with same volume of normal saline. The cardiac function and serum cardiac troponin I (cTnI) level of each group was measured. HE staining and HBFP staining were used to evaluate the myocardial micro-infarction area of myocardium tissue samples. Then RT-qPCR and western blot were used to detect the expression of miR-30e-3p and, autophagy related protein LC3-II and p62, respectively. Transmission electron microscope (TEM) was used to identify autophagic vacuoles in tissue samples. Results: The cardiac function of the CME 6h,9h, and 12h groups were significantly decreased compared to the sham group (P < 0.05) and the cTnI level in each group were also significantly increased (P < 0.05). The expression of miR-30e-3p in the CME 6h, 9h and 12h group were decreased significantly compared with the sham group (P < 0.05). Meanwhile, the expression of autophagy related protein LC3-II decreased significantly and p62 increased significantly in the CME 9h and 12h group (P < 0.05). TEM images showed typical autophagic vacuoles for each of the CME groups. Conclusions: Myocardial miR-30e-3p is down regulated after CME and is accompanied by inhibited autophagy and decreased cardiac function. Therefore, miR-30e-3p may be involved in CME-induced cardiac dysfunction by regulating myocardial autophagy.

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“…Furthermore, it was found in rats that prolonged hypoxia exposure over a period of 10 days resulted in a significant alteration in gene expression as evident through quantitative detection of various microRNAs. The administration of the DOR agonist UFP-512 mimicked hypoxic conditions effects on multiple miRNA molecules through potentiated expression while reduced others (23) . Observed results indicate the complex pathways mediated by DOR activation that with further investigations might lead to a better understanding of the molecular basis of DOR roles and potentially provide therapeutic targets in the control and management of ischemic heart diseases (IHD).…”

Section: Dor Cardioprotective Effectsmentioning

confidence: 99%

Promising Therapeutic Agents: Delta Opioid Receptor Agonists

Bazzari

2017

IAM

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Adequate characterization of the endogenous opioid system's peptides and receptors; in addition to, the development of highly selective ligands, have improved research approaches and understanding the roles of this system. DeltaOpioid Receptor (DOR) was found to exhibit distinctive pharmacological profile and tissue distribution compared to other opioid receptors. Hence, DOR has been extensively investigated in the last decade as a potential target in the treatment of various disorders. Research findings indicate high potential of DOR agonists in the modulation of brain as well as cardiovascular system functions. DOR activation was found to display cytoprotective effects against ischemia/reperfusion injury in neurons and cardiomyocytes. DOR affects cellular functions on the level of gene expression, ion channels, enzymatic activity and membrane-receptors functions through multiple signaling pathways and second messenger systems. Moreover, DOR has been implicated in mood disorders; in vivo administration of DOR agonists and enkephalinase inhibitors had significant anxiolytic and antidepressant effects. More recent research findings have shown consistent and statistically significant results on DOR activation beneficial effects in cardiac conditioning, neural ischemia protection, anxiety and depression management. Further advances in research would potentially reveal the exact molecular mechanisms underlying DOR functions in relation to receptor subtypes and signaling pathways.

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δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

Cited by 25 publications

References 52 publications

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

Promising Therapeutic Agents: Delta Opioid Receptor Agonists

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