MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury

Abstract

A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium

“…The detailed process mainly referred to previous documents. 25 To measure the change, we added QUE and QUE/P in HUVECs, and treated by tumor necrosis factor-α (TNF-α), added carboxyfluorescein diacetate succinimidyl ester-labeled acute promyelocytic leukemia (HL-60) leukocytes, washed the mixtures, and checked leukocyte binding to the ECs. Neutrophil adhesion in vivo was observed by immunofluorescence microscopy method.…”

“…23,24 As a result, CD11b + associates with its counter receptors on ECs, mainly ICAM-1, leading to their firm adhesion and transmigration by vascular wall. 25,26 Substantial evidence indicates that expression of adhesion molecules via glomerular ECs is increased following DN. 17,27,28 Therefore, understanding discovery of ECs will improve the effective therapies, which can be applied in DN procedure.…”

“…+ cells infiltration (referred to previous literature 25 ), and expression of ICAM-1 (referred to previous literature 25 ) were evaluated.…”

Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway

“…38 With the discovery of circRNAs as miRNA sponges, it is tempting to speculate that mcircRasGEF1B could sequester miRNAs targeting ICAM-1. The expression of ICAM-1 has been shown to be regulated by several miRNAs, including miR-223, 39 miR-141, 40 and miR-296-3p. 41 However, sequence analysis of mcircRasGEF1B does not reveal any enrichment of multiple ( 3) binding sites for any known miRNAs within mcircRasGEF1B, and it harbors no binding sites for miR-223, miR-141 and miR-296-3p (data not shown).…”

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside protects murine hearts against ischemia/reperfusion injury by activating Notch1/Hes1 signaling and attenuating endoplasmic reticulum stress

“…The TSG dose was selected based on previous studies [16,27,28] . Two weeks after the treatment, MI/R surgery was performed as previously described [29] . Briefly, C57Bl/6 mice were anesthetized with 1% pentobarbital sodium.…”