IFN-γ enhances the efficacy of mesenchymal stromal cell-derived exosomes via miR-21 in myocardial infarction rats

Zhang, Jian; Lu, Yao; Mao, Yangming; Yu, Yue; Wu, Tianyu; Zhao, Wei; Zhu, Yeqian; Zhao, Pengcheng; Zhang, Fengxiang

doi:10.1186/s13287-022-02984-z

Cited by 45 publications

(35 citation statements)

References 34 publications

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“…DOX causes myocardial injury, to which OS and pyroptosis were closely linked 30,31 . Recent research revealed that MSC‐derived Exos protect against myocardial infarction and myocardial ischemia–reperfusion injury, so increasing attention is paid to their potential therapeutic values in treating myocardial problems 32,33 . To probe the specific role of BMSC‐Exos in DOX cardiotoxicity, this study was conducted to ascertain the function of BMSC‐Exos in OS and pyroptosis during DOX‐induced myocardial injury and the related mechanism.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow stromal cell‐derived exosomes improve oxidative stress and pyroptosis in doxorubicin‐induced myocardial injury in vitro by regulating the transcription of GSDMD through the PI3K‐AKT‐Foxo1 pathway

Zeng

Yang

Tou

et al. 2023

Immunity Inflam & Disease

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Objectives Doxorubicin (DOX) can contribute to severe myocardial injury, and bone marrow stromal cells (BMSC)‐exosomes (Exos) improves acute myocardial infarction. Hence, this research investigated whether BMSC‐Exos alleviated DOX‐induced myocardial injury. Methods BMSC‐derived Exos were isolated and identified, and the optimal concentration of DOX was confirmed. H9C2 cells were treated with DOX and BMSC‐Exos or in combination with the protein kinase B (AKT) inhibitor. Reactive oxygen species (ROS) and JC‐1 were detected to assess oxidative stress (OS) and mitochondrial membrane damage, respectively. In addition, the expression of pyroptosis‐related molecules was measured. The expression of phosphatidylinositol 3 kinase (PI3K)‐AKT pathway‐related proteins and the phosphorylation and acetylation of forkhead box O1 (Foxo1) in the cell nucleus and cytoplasm were tested. Last, interactions between Foxo1 and gasdermin D (GSDMD) were assessed. Results BMSC‐Exo treatment increased viability and mitochondrial membrane potential and reduced lactic dehydrogenase release and ROS levels in DOX‐treated H9C2 cells. Furthermore, the addition of BMSC‐Exos suppressed DOX‐induced activation and upregulation of NLRP3 and apoptosis‐associated speck‐like protein containing A CARD (ASC) and in vitro cleavage of caspase‐1, GSDMD, interleukin (IL)‐1β, and IL‐18 proteins. Additionally, BMSC‐Exo treatment enhanced the expression of phosphorylated (p)‐PI3K, p‐AKT, and p‐mTOR in DOX‐treated H9C2 cells and the levels of phosphorylated Foxo1 in the cytoplasm of DOX‐treated H9C2 cells. Foxo1 was enriched in the promoter region of GSDMD. Moreover, the AKT inhibitor API‐2 annulled the effects of BMSC‐Exos on OS, pyroptosis, and Foxo1 phosphorylation in DOX‐treated H9C2 cells. Conclusions BMSC‐Exos phosphorylated Foxo1 and inactivated Foxo1 transcription via the PI3K‐AKT pathway to diminish GSDMD expression, thus restraining DOX‐induced pyroptosis and OS of myocardial cells.

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Section: Discussionmentioning

confidence: 99%

Bone marrow stromal cell‐derived exosomes improve oxidative stress and pyroptosis in doxorubicin‐induced myocardial injury in vitro by regulating the transcription of GSDMD through the PI3K‐AKT‐Foxo1 pathway

Zeng

Yang

Tou

et al. 2023

Immunity Inflam & Disease

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“…Recently, it has been shown that exposing MSCs to interferon-gamma (IFN-γ) improved their therapeutic effect. The improved cardiac outcome, cardiomyocyte survival, reduced fibrotic scarring, and increased angiogenesis were associated with exosomes carrying miR-21a [79]. In hepatocytes, miR-21a has been shown to play a role in lipid metabolism [80].…”

Section: Myocardial Infarction and Strokesmentioning

confidence: 99%

Exosomes and lipid metabolism in metabolic and cardiovascular disorders

Abdin¹,

Geng²,

Chandy

2023

Current Opinion in Lipidology

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Purpose of reviewExosomes are lipid-bound particles that carry lipids, protein, and nucleic acid and affect cellular function. This review highlights the current knowledge on the crosstalk between exosomes and lipid metabolism and their impact on cardiometabolic disease.Recent findingsRecent studies revealed that lipids and lipid metabolizing enzymes are important for exosome biogenesis and internalization and conversely how exosomes affect lipid metabolism, secretion, and degradation. The interplay between exosomes and lipid metabolism affects disease pathophysiology. More importantly, exosomes and lipids might function as biomarkers for diagnosis and prognosis or possibly therapies.SummaryRecent advances in our understanding of exosomes and lipid metabolism have implications for our understanding of normal cellular and physiological functions as well as disease pathogenesis. Exosome and lipid metabolism have implications in novel diagnostic tests and treatments of cardiometabolic disease.

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“…Zhang et al obtained IFN-γ-loaded MSC-EVs by coculturing IFN-γ with MSCs. Then, IFN-γ-loaded MSC-EVs were used to treat a mouse MI model in the infarction region, increasing the amount of miRNA-21 and causing decreased fibrosis, reduced apoptosis of cardiomyocytes, and improved cardiac function [152].…”

Section: Loading Specific Molecules Into Evsmentioning

confidence: 99%

Can Extracellular Vesicles as Drug Delivery Systems Be a Game Changer in Cardiac Disease?

et al. 2022

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Cardiac diseases such as myocardial infarction and heart failure have been the leading cause of death worldwide for more than 20 years, and new treatments continue to be investigated. Heart transplantation, a curative treatment for severe cardiac dysfunction, is available to only a small number of patients due to the rarity of donors and high costs. Cardiac regenerative medicine using embryonic stem cells and induced pluripotent stem cells is expected to be a new alternative to heart transplantation, but it has problems such as induction of immune response, tumor formation, and low survival rate of transplanted cells. On the other hand, there has been a focus on cell-free therapy using extracellular vesicles (EVs) due to their high biocompatibility and target specificity. Exosomes, one type of EV, play a role in the molecular transport system in vivo and can be considered a drug delivery system (DDS) innate to all living things. Exosomes contain nucleic acids and proteins, which are transported from secretory cells to recipient cells. Molecules in exosomes are encapsulated in a lipid bilayer, which allows them to exist stably in body fluids without being affected by nuclease degradation enzymes. Therefore, the therapeutic use of exosomes as DDSs has been widely explored and is being used in clinical trials and other clinical settings. This review summarizes the current topics of EVs as DDSs in cardiac disease.

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IFN-γ enhances the efficacy of mesenchymal stromal cell-derived exosomes via miR-21 in myocardial infarction rats

Cited by 45 publications

References 34 publications

Bone marrow stromal cell‐derived exosomes improve oxidative stress and pyroptosis in doxorubicin‐induced myocardial injury in vitro by regulating the transcription of GSDMD through the PI3K‐AKT‐Foxo1 pathway

Bone marrow stromal cell‐derived exosomes improve oxidative stress and pyroptosis in doxorubicin‐induced myocardial injury in vitro by regulating the transcription of GSDMD through the PI3K‐AKT‐Foxo1 pathway

Exosomes and lipid metabolism in metabolic and cardiovascular disorders

Can Extracellular Vesicles as Drug Delivery Systems Be a Game Changer in Cardiac Disease?

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