Olfactory mucosal mesenchymal stem cell-derived exosome Lnc A2M-AS1 ameliorates oxidative stress by regulating TP53INP1-mediated mitochondrial autophagy through interacting with IGF2BP1 in Parkinson's diseases.

IF 5.3 2区医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2025-03-20 DOI:10.1007/s10565-025-10009-7

Jiangshan Zhang, Chuang Wang, Guoshuai Yang, Yanhui Zhou, Dan Hou, Ying Xia

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引用次数: 0

Abstract

Background: Exosome Lnc A2M-AS1 from olfactory mucosa mesenchymal stem cells (OM-MSCs) can ameliorate oxidative stress by improving mitophagy in cardiomuscular cells; however, it remains unclear whether this effect exists in the brain tissues of patients with Parkinson's disease (PD).

Methods: OM-MSC-Exosomes were isolated and verified based on morphology and specific biomarkers. The effects of OM-MSC-Exo on mitochondrial autophagy, oxidative stress, and lncRNA A2M-AS1 were detected in MPP⁺-treated HT22 cells. The effects of OM-MSC-Exos on mitochondrial autophagy and oxidative stress were detected in an MPTP-induced Parkinson's disease (PD) model in C57BL/6 mice. The interaction between IGF2BP1, A2M-AS1, and TP53INP1 was assessed via RNA pull-down/RNA Immunoprecipitation and RNA stability assays. The effects of lnc A2M-AS1 on IGF2BP1/TP53INP1-mediated mitochondrial autophagy and oxidative stress were verified in MPP⁺-treated HT22 cells and MPTP-induced PD mouse models.

Results: Exosomes isolated from olfactory mucosa mesenchymal stem cells were found to be rich in Lnc A2M-AS1. Lnc A2M-AS1 was proved to be able to ameliorate oxidative stress induced by MPP⁺ in HT22 cells. lncRNA A2M-AS1 regulates oxidative stress by enhancing mitophagy in HT22 cells. In addition, lncRNA A2M-AS1 induced mitophagy through TP53INP1 and mediated TP53INP1 expression by binding to IGF2BP1. Furthermore, OM-MSC-Exo and Lnc A2M-AS1 treatment improved symptoms and ameliorated oxidative stress in MPTP-induced PD mouse models.

Conclusion: Collectively, lncRNA A2M-AS1 from OM-MSC-derived exosomes regulates TP53INP1 expression by targeting IGF2BP1 to induce mitophagy and ameliorate oxidative stress. OM-MSC-derived exosomes could potentially serve as promising candidates for new treatment methods for PD.

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来源期刊

Cell Biology and Toxicology 生物-毒理学

CiteScore

9.90

自引率

4.90%

发文量

101

审稿时长

>12 weeks

期刊介绍： Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.