Down-Regulation of miR-327 Alleviates Ischemia/Reperfusion-Induced Myocardial Damage by Targeting RP105

Abstract Background/Aims: Micro RNAs (miRNAs) play a very important role in myocardial ischemia/ reperfusion injury (MIRI), including in inflammation, apoptosis, and angiogenesis. Previous studies have demonstrated up-regulation of miR-327 in renal ischemia/reperfusion injury and MIRI. Via TargetSca...

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Published in:Cellular physiology and biochemistry Vol. 49; no. 3; pp. 1090 - 1104
Main Authors: Yang, Ying, Yang, Jun, Liu, Xiao-wen, Ding, Jia-wang, Li, Song, Guo, Xin, Yang, Chao-jun, Fan, Zhi-xin, Wang, Hui-bo, Li, Qi, Wang, Hui-min, Yang, Jian
Format: Journal Article
Language:English
Published: Basel, Switzerland S. Karger AG 01-01-2018
Cell Physiol Biochem Press GmbH & Co KG
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Summary:Abstract Background/Aims: Micro RNAs (miRNAs) play a very important role in myocardial ischemia/ reperfusion injury (MIRI), including in inflammation, apoptosis, and angiogenesis. Previous studies have demonstrated up-regulation of miR-327 in renal ischemia/reperfusion injury and MIRI. Via TargetScan, we found RP105 is a possible target gene of miR-327; our previous studies have also confirmed that RP105 acted as a cardioprotective protein in MIRI by reducing inflammation. However, the regulatory effect of miR-327 on RP105 has not previously been proposed. In our study, we aimed to identify the regulatory effect of miR-327 on RP105 protein in MIRI rats. Methods: Sixty male Sprague–Dawley rats were randomly divided into five groups, which were pre-treated with saline (sham and ischemia/reperfusion group), adenovirus-expressing miR-327-RNAi (Ad-miR-327-i group), control (Ad-NC group), or pri-miR-327 (Ad-miR-327 group) treatments. Three days later, the rat MIRI model was established by ischemia for 30 min, followed by reperfusion for 3 h. Myocardium and plasma were harvested and assessed. Results: miR-327 was increased by nearly 3-fold both in myocardium and plasma, which down-regulated RP105 in a 3′-untranslated region-dependent manner, and down-regulation of miR-327 via adenovirus transfection indirectly suppressed the TLR4/ TLR2-MyD88-NF-κB signaling axis activation via up-regulation of RP105, which subsequently resulted in reduced myocardial infarct size, attenuated cardiomyocyte destruction, and alleviated inflammation. In contrast, up-regulation of miR-327 induced the opposite effect. Conclusion: Down-regulation of miR-327 exerts a cardioprotective effect against MIRI by reducing inflammation, which may constitute a promising molecular therapeutic target for treating MIRI.
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ISSN:1015-8987
1421-9778
DOI:10.1159/000493288