Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation

作者：Fengdan Wang, Yi Ding, Jianhong Zhou, En Zhou, Tiantian Zhang, Yu-Qi Fan, Qing He, Zongqi Zhang, Cheng-Yu Mao, Junfeng Zhang, Jing Zhou · 发表于：World Journal of Stem Cells · 年份：2024 · DOI：10.4252/wjsc.v16.i10.873 · 被引用次数：5 · 研究领域：Cardiac Fibrosis and Remodeling、Cardiac Ischemia and Reperfusion、Redox biology and oxidative stress

BACKGROUND Myocardial ischemia-reperfusion injury (MIRI) poses a prevalent challenge in current reperfusion therapies, with an absence of efficacious interventions to address the underlying causes. AIM To investigate whether the extracellular vesicles (EVs) secreted by adipose mesenchymal stem cells (ADSCs) derived from subcutaneous inguinal adipose tissue (IAT) under γ-aminobutyric acid (GABA) induction (GABA-EVsIAT) demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms. METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA. We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays. The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds. To explore the functional RNA diversity between EVsIAT and GABA-EVsIAT, we employed microRNA (miR) sequencing. Through a dual-luciferase reporter assay, we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein (TXNIP). Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction. RESULTS Our study demonstrates that, under the influence of GABA, ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs. Con...