دورية أكاديمية
Protective Role of lncRNA TTN-AS1 in Sepsis-Induced Myocardial Injury Via miR-29a/E2F2 Axis.
| العنوان: | Protective Role of lncRNA TTN-AS1 in Sepsis-Induced Myocardial Injury Via miR-29a/E2F2 Axis. |
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| المؤلفون: | Pei X; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China., Wu Y; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China., Yu H; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China., Li Y; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China., Zhou X; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China., Lei Y; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China., Lu W; Department of Critical Care Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, West Jiefang Road, Furong District, Hunan, 410005, Changsha, People's Republic of China. luwu1979aa@163.com. |
| المصدر: | Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2022 Jun; Vol. 36 (3), pp. 399-412. Date of Electronic Publication: 2021 Sep 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Kluwer Academic For The International Society For Cardiovascular Pharmacotherapy Country of Publication: United States NLM ID: 8712220 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7241 (Electronic) Linking ISSN: 09203206 NLM ISO Abbreviation: Cardiovasc Drugs Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Norwell Ma : Kluwer Academic For The International Society For Cardiovascular Pharmacotherapy Original Publication: [Norwell, MA] : Martinus Nijhoff Pub., [c1987- |
| مواضيع طبية MeSH: | E2F2 Transcription Factor* , MicroRNAs*/genetics , MicroRNAs*/metabolism , RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , Sepsis*/complications , Sepsis*/genetics , Sepsis*/metabolism, Animals ; Humans ; Rats ; Apoptosis ; Connectin ; Lipopolysaccharides/pharmacology ; Reactive Oxygen Species |
| مستخلص: | Objective: Approximately 50% of patients with sepsis encounter myocardial injury. The mortality of septic patients with cardiac dysfunction (approx. 70%) is much higher than that of patients with sepsis only (20%). A large number of studies have suggested that lncRNA TTN-AS1 promotes cell proliferation in a variety of diseases. This study delves into the function and mechanism of TTN-AS1 in sepsis-induced myocardial injury in vitro and in vivo. Methods: LPS was used to induce sepsis in rats and H9c2 cells. Cardiac function of rats was assessed by an ultrasound system. Myocardial injury was revealed by hematoxylin-eosin (H&E) staining. Gain and loss of function of TTN-AS1, miR-29a, and E2F2 was achieved in H9c2 cells before LPS treatment. The expression levels of inflammatory cytokines and cTnT were monitored by ELISA. The expression levels of cardiac enzymes as well as reactive oxygen species (ROS) activity and mitochondrial membrane potential (MMP) were measured using the colorimetric method. The expression levels of TTN-AS1, miR-29a, E2F2, and apoptosis-related proteins were measured by RT-qPCR and/or western blotting. The proliferation and apoptosis of H9c2 cells were separately detected by CCK-8 and flow cytometry. Luciferase reporter assay was used to verify the targeting relationships among TTN-AS1, miR-29a and E2F2, and RIP assay was further used to confirm the binding between miR-29a and E2F2. Results: TTN-AS1 was lowly expressed, while miR-29a was overexpressed in the cell and animal models of sepsis. Overexpression of TTN-AS1 or silencing of miR-29a reduced the expression levels of CK, CK-MB, LDH, TNF-B, IL-1B, and IL-6 in the supernatant of LPS-induced H9c2 cells, attenuated mitochondrial ROS activity, and enhanced MMP. Consistent results were observed in septic rats injected with OE-TTN-AS1. Knockdown of TTN-AS1 or overexpression of miR-29a increased LPS-induced inflammation and injury in H9c2 cells. TTN-AS1 regulated the expression of E2F2 by targeting miR-29a. Overexpression of miR-29a or inhibition of E2F2 abrogated the suppressive effect of TTN-AS1 overexpression on myocardial injury. Conclusion: This study indicates TTN-AS1 attenuates sepsis-induced myocardial injury by regulating the miR-29a/E2F2 axis and sheds light on lncRNA-based treatment of sepsis-induced cardiomyopathy. (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.) |
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| فهرسة مساهمة: | Keywords: Cardiomyopathy; E2F2; Sepsis; TTN-AS1; miR-29a |
| المشرفين على المادة: | 0 (Connectin) 0 (E2F2 Transcription Factor) 0 (Lipopolysaccharides) 0 (MicroRNAs) 0 (MIRN29 microRNA, rat) 0 (Reactive Oxygen Species) 0 (RNA, Long Noncoding) 0 (Ttn protein, rat) |
| تواريخ الأحداث: | Date Created: 20210914 Date Completed: 20221229 Latest Revision: 20221229 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1007/s10557-021-07244-5 |
| PMID: | 34519914 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1573-7241 |
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| DOI: | 10.1007/s10557-021-07244-5 |