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δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia
Feng Zhi1, Lian Xue, Naiyuan Shao
1Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
Background:
Hypoxic/ischemic injury to the heart is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ischemic events, and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering miRNA expression in the heart under hypoxic conditions. The present study aimed to test our hypothesis.
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 from TaqMan low-density array (TLDA) data and were further analyzed by quantitative real-time PCR.
Results:
We found that: 1) hypoxia alters the miRNA expression profiles depending on the hypoxic duration; 2) DOR activation shifts miRNA expression profiles in normoxic conditions and upregulates miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, and miR-338; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression and increases the levels of miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, miR-141, miR-200b, and miR-324-3p. For example, miR-196c-5p decreased by 50% while miR-135a-5p increased 2.9 fold after 10 days under hypoxic conditions. Moreover, DOR activation further strengthened the hypoxia-induced increase of the levels of miR-7a-5p. When DOR was activated using UFP-512, the level of miR-107-3p significantly increased 1 day after the administration of UFP-512, but gradually decreased back to normal under normoxia.
Conclusion:
Hypoxia significantly modifies the miRNA profile in the heart, which can be mimicked or modified by DOR activation. Defining the targeted pathways that regulate the diverse cellular and molecular functions of miRNAs may provide new insights into potential therapies for hypoxic/ischemic injury of the heart.
Insights
Hypoxic heart injury alters microRNA (miRNA) profiles, and delta-opioid receptor (DOR) activation can modify these changes. This suggests DOR activation may offer new therapeutic strategies for heart conditions.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Hypoxic/ischemic heart injury presents significant clinical challenges with limited treatment options.
- MicroRNAs (miRNAs) play a role in hypoxic/ischemic events.
- Delta-opioid receptor (DOR) activation is known to be cardioprotective.
Purpose of the Study:
- To investigate the hypothesis that DOR activation alters miRNA expression in the heart during hypoxia.
- To understand the impact of DOR activation on miRNA profiles under both normoxic and hypoxic conditions.
Main Methods:
- Male Sprague Dawley rats were subjected to hypoxia (9.5-10% O2) for varying durations (1, 5, or 10 days).
- DOR activation was administered with or without hypoxic exposure.
- miRNA expression was analyzed using TaqMan low-density arrays and quantitative real-time PCR.
Main Results:
- Hypoxia alters cardiac miRNA expression profiles in a duration-dependent manner.
- DOR activation alone modulated miRNA profiles and upregulated specific miRNAs (e.g., miR-128a-3p, miR-134-5p, miR-135a).
- DOR activation modified hypoxia-induced miRNA changes, increasing levels of several miRNAs and potentiating hypoxia-induced increases in others.
Conclusions:
- Hypoxia significantly alters cardiac miRNA profiles.
- DOR activation can mimic or modify these hypoxia-induced miRNA changes.
- Identifying targeted pathways regulated by these miRNAs may lead to novel therapies for hypoxic/ischemic heart injury.
