Liver‐Secreted Extracellular Vesicles Promote Cirrhosis‐Associated Skeletal Muscle Injury Through mtDNA‐cGAS/STING Axis

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Skeletal muscle atrophy (sarcopenia) is a serious complication of liver cirrhosis, and chronic inflammation plays pivotal role in its pathologenesis. However, the detailed mechanism through which injured tissues mediate skeletal inflammatory injury remains elusive. Here, it reported that hepatocytes might secrete mtDNA‐enriched extracellular vesicles (EVs) to trigger by activating cGAS‐STING pathway. Briefly, secreted increased amounts EVs into circulation, are then engulfed primarily macrophages subsequently induce signaling its‐mediated response muscles. In contrast, suppression hepatic EV secretion or STING significantly alleviated cirrhosis‐induced vivo. Circulating from cirrhotic patients showed higher levels mtDNA, EV‐mtDNA positively correlated with severity injury. hepatocytes, mitochondrial damage promoted release cytosolic mtDNA subsequent EVs. This study reveals hepatocyte‐derived via mtDNA‒STING axis, while targeted blockade represents potential therapeutic approach for preventing cirrhosis‐associated atrophy.

Язык: Английский

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Extracellular vesicle-mediated bidirectional communication between the liver and other organs: mechanistic exploration and prospects for clinical applications

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 8, 2025

The liver, functioning as an endocrine organ, secretes a variety of substances that influence the activities other body organs. Conversely, molecules generated by organs such bone, gut, and adipose tissue can also impact liver function. Accumulating evidence suggests bidirectional communication between However, research on how extracellular vesicles (EVs), which transport active molecular mediators, contribute to this interorgan is still in its nascent stages. EVs are capable transporting functional molecules, including lipids, nucleic acids, proteins, thereby affecting recipient cells across different at biological level. This review examines role facilitating cardiovascular system, pancreas, brain, lungs, kidneys, tissue. It explores their potential disease treatment highlights challenges understanding EV-mediated interactions. contribution mediator-carrying two-way remains area ongoing investigation. Future will provide more comprehensive theoretical foundation clarify precise mechanisms governing organs, pinpoint medical targets, expand application within realm precision medicine.

Язык: Английский

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Native and Engineered Extracellular Vesicles for the Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Small Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Extracellular vesicles (EVs) are lipid bilayer nanoparticles naturally released from cells, playing a crucial role in intercellular communication. They modulate gene expression and regulate physiological pathological processes, including acute lung injury (ALI) respiratory distress syndrome (ARDS). Research has shown that EVs contain variety of active components, biocompatible small size, do not trigger immune rejection, making the infusion exogenous promising therapeutic tool. With further research, engineering strategies have been proposed to enhance clinical potential EVs. These involve modifying either donor cells secrete or themselves can be engineered circumvent limitations native In this review, an overview biological properties is provided current treating ALI/ARDS, along with latest research findings, summarized. The challenges opportunities for translation as novel tool also discussed, offering new insights into treatment ALI/ARDS using EV technology.

Язык: Английский

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In Vivo Reprogramming of Tissue‐Derived Extracellular Vesicles for Treating Chronic Tissue Injury Through Metabolic Engineering

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Extracellular vesicles (EVs) have emerged as promising therapeutics for regenerative medicine, but the efficacy of current exogenous EV-based therapies treating chronic tissue injury is still unsatisfactory. Exercise can affect skeletal muscle EV secretion and that this process regulates systemic health-promoting role exercise, suggesting fine-tuning endogenous may provide a new therapeutic avenue. Here, work reports in vivo reprogramming via metabolic engineering strategy diseases. Briefly, exercise enhanced mitochondrial metabolism production healthy muscles, EVs from muscles subjected to or (boosting biogenesis AAV-mediated muscle-specific TFAM overexpression) exerted cellular protective effects vitro. In injured therapy could reprogram patterns (reducing pathological compositions while increasing beneficial compositions) by regulating multiple cargo sorting pathways. Reprogrammed muscle-derived reach major organs tissues circulation then simultaneously attenuated multiple-tissue (e.g., kidney) kidney disease. This study highlights tissue-derived approach potential diverse

Язык: Английский

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Unveiling the functional heterogeneity of endogenous tissue extracellular vesicles in skeletal muscle through multi-omics

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 162679 - 162679

Опубликована: Апрель 1, 2025

Язык: Английский

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Single extracellular vesicle research: From cell population to a single cell

Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 734, С. 150439 - 150439

Опубликована: Июль 23, 2024

Язык: Английский

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Disease-derived circulating extracellular vesicle preconditioning: A promising strategy for precision mesenchymal stem cell therapy

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(10), С. 4526 - 4543

Опубликована: Июнь 28, 2024

Mesenchymal stem cell (MSC)-based therapies have emerged as promising methods for regenerative medicine; however, how to precisely enhance their tissue repair effects is still a major question in the field. Circulating extracellular vesicles (EVs) from diseased states carry diverse pathological information and affect functions of recipient cells. Based on this unique property, we report that disease-derived circulating EV (disease-EV) preconditioning potent strategy enhancing potency MSCs disease models. Briefly, plasma EVs lung or kidney injuries were shown contain distinctly enriched molecules induce injury-specific gene expression responses cultured MSCs. Disease-EV improved performance (including proliferation, migration, growth factor production) through metabolic reprogramming (such

Язык: Английский

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The role and clinical applications of exosomes in cancer drug resistance

Cancer Drug Resistance, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Tumor-secreted exosomes are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating intercellular crosstalk activating signaling pathways. Distinct from previous reviews, we focus intently on exosome-therapeutic resistance dynamics summarize the new findings about regulation of treatment exosomes, shedding light complex processes via which these nanovesicles facilitate therapeutic refractoriness across various malignancies. Future research in exosome biology can potentially transform diagnostic paradigms interventions for management. This review synthesizes recent insights into exosome-driven drug resistance, illuminates sophisticated mechanisms malignancies, summarizes some strategies to overcome resistance.

Язык: Английский

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Extracellular Vesicles and Bacterial Infection

Опубликована: Янв. 1, 2024

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The role of macrophage-derived exosomes in noncancer liver diseases: From intercellular crosstalk to clinical potential

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113437 - 113437

Опубликована: Окт. 24, 2024

Язык: Английский

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