MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury
| العنوان: | MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury |
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| المؤلفون: | Yu Si Zhang, Chao jun Song, Rongrong Liu, Fang Kuang, Lihua Chen, Bo Quan Jin, Agnieszka D. Truax, Jun Li, Feng Gao, Qianli Ma, Jiu Yu Gong, Kun Yang, Jia Yun Liu |
| المصدر: | American Journal of Physiology-Heart and Circulatory Physiology. 309:H1303-H1313 |
| بيانات النشر: | American Physiological Society, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Time Factors, Endothelium, Physiology, Myocardial Infarction, HL-60 Cells, Myocardial Reperfusion Injury, Transfection, chemistry.chemical_compound, Physiology (medical), Lactate dehydrogenase, Troponin I, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Leukocytes, medicine, Animals, Humans, RNA, Messenger, 3' Untranslated Regions, Regulation of gene expression, Mice, Inbred BALB C, ICAM-1, biology, Tumor Necrosis Factor-alpha, Macrophages, Myocardium, Endothelial Cells, Genetic Therapy, Intercellular Adhesion Molecule-1, medicine.disease, Molecular biology, Coculture Techniques, Disease Models, Animal, MicroRNAs, medicine.anatomical_structure, Gene Expression Regulation, Integrin alpha M, chemistry, biology.protein, Cancer research, Female, Tumor necrosis factor alpha, Cardiology and Cardiovascular Medicine, Reperfusion injury |
| الوصف: | 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. |
| تدمد: | 1522-1539 0363-6135 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::86fc98060b48fed3bfa1759f2e5fbce9Test https://doi.org/10.1152/ajpheart.00290.2015Test |
| رقم الانضمام: | edsair.doi.dedup.....86fc98060b48fed3bfa1759f2e5fbce9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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