دورية أكاديمية
أعرض في EDS

Secretion of miRNA-326-3p by senescent adipose exacerbates myocardial metabolism in diabetic mice.

التفاصيل البيبلوغرافية
العنوان: Secretion of miRNA-326-3p by senescent adipose exacerbates myocardial metabolism in diabetic mice.
المؤلفون: Lin H; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Chen X; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Pan J; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Ke J; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Zhang A; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Liu Y; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Wang C; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China., Chang ACY; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. alexchang@shsmu.edu.cn.; Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. alexchang@shsmu.edu.cn., Gu J; Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. gjforsub@163.com.
المصدر: Journal of translational medicine [J Transl Med] 2022 Jun 21; Vol. 20 (1), pp. 278. Date of Electronic Publication: 2022 Jun 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2003-
مواضيع طبية MeSH: Diabetes Mellitus, Experimental*/complications , Diabetic Cardiomyopathies*/metabolism , MicroRNAs*/genetics , MicroRNAs*/metabolism, Adipose Tissue/metabolism ; Animals ; Cells, Cultured ; Humans ; Mice ; Myocytes, Cardiac/pathology
مستخلص: Background: Adipose tissue homeostasis is at the heart of many metabolic syndromes such as diabetes. Previously it has been demonstrated that adipose tissues from diabetic patients are senescent but whether this contributes to diabetic cardiomyopathy (DCM) remains to be elucidated.
Methods: The streptozotocin (STZ) type 1 diabetic mice were established as animal model, and adult mouse ventricular myocytes (AMVMs) isolated by langendorff perfusion as well as neonatal mouse ventricular myocytes (NMVMs) were used as cell models. Senescent associated β galactosidase (SA-β-gal) staining and RT-qPCR were used to identify the presence of adipose senescence in diabetic adipose tissue. Senescent adipose were removed either by surgery or by senolytic treatment. Large extracellular vesicles (LEVs) derived from adipose tissue and circulation were separated by ultracentrifugation. Cardiac systolic and diastolic function was evaluated through cardiac ultrasound. Cardiomyocytes contraction function was evaluated by the Ionoptix HTS system and live cell imaging, mitochondrial morphology and functions were evaluated by transmission electron microscope, live cell fluorescent probe and seahorse analysis. RNA-seq for AMVMs and miRNA-seq for LEVs were performed, and bioinformatic analysis combined with RT-qPCR and Western blot were used to elucidate underlying mechanism that senescent adipose derives LEVs exacerbates myocardial metabolism.
Results: SA-β-gal staining and RT-qPCR identified the presence of adipose tissue senescence in STZ mice. Through surgical as well as pharmacological means we show that senescent adipose tissue participates in the pathogenesis of DCM in STZ mice by exacerbates myocardial metabolism through secretion of LEVs. Specifically, expression of miRNA-326-3p was up-regulated in LEVs isolated from senescent adipose tissue, circulation, and cardiomyocytes of STZ mice. Up-regulation of miRNA-326-3p coincided with myocardial transcriptomic changes in metabolism. Functionally, we demonstrate that miRNA-326-3p inhibited the expression of Rictor and resulted in impaired mitochondrial and contractile function in cardiomyocytes.
Conclusion: We demonstrate for the first time that senescent adipose derived LEVs exacerbates myocardial metabolism through up-regulated miRNA-326-3p which inhibits Rictor in cardiomyocytes. Furthermore, reducing senescence burden in adipose tissue is capable of relieving myocardial metabolism disorder in diabetes mellitus.
(© 2022. The Author(s).)
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فهرسة مساهمة: Keywords: Adipose tissue; Cardiomyocytes; Diabetic cardiomyopathy; Extracellular vesicles; Senescence
المشرفين على المادة: 0 (MIRN326 microRNA, human)
0 (MicroRNAs)
تواريخ الأحداث: Date Created: 20220621 Date Completed: 20220623 Latest Revision: 20240830
رمز التحديث: 20240830
مُعرف محوري في PubMed: PMC9210699
DOI: 10.1186/s12967-022-03484-7
PMID: 35729559
قاعدة البيانات: MEDLINE
الوصف
تدمد:1479-5876
DOI:10.1186/s12967-022-03484-7