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

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 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.

Language: Английский

Unraveling the Metabolic Pathways Between Metabolic-Associated Fatty Liver Disease (MAFLD) and Sarcopenia

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4673 - 4673

Published: May 14, 2025

Metabolic-Associated Fatty Liver Disease (MAFLD) is a public health concern that constantly expanding, with fast-growing prevalence, and it affects about quarter of the world's population. This condition significant risk factor for cardiovascular, hepatic, oncologic diseases, such as hypertension, hepatoma, atherosclerosis. Sarcopenia was long considered to be an aging-related syndrome, but today, acknowledged secondarily related chronic diseases metabolic cardiovascular conditions, liver among other comorbidities associated insulin resistance inflammation, besides inactivity poor nutrition. The physiopathology involving MAFLD sarcopenia has still not been solved. Inflammation, oxidative stress, mitochondrial dysfunction, seem some keys this relationship since hormone target mainly skeletal muscle. review aimed comprehensively discuss main physiological pathways involved in these conditions. are interconnected by complex network pathophysiological mechanisms, resistance, muscle tissue production capacity, inflammatory state, which contributors relationship. In addition, clinical analysis, patients manifest more severe hepatitis fibrosis when compared only MAFLD. These patients, both disorders, also present improvement their treated sarcopenia, reinforcing association between them. Lifestyle changes accompanied non-pharmacological interventions, dietary therapy increased physical activity, undoubtedly improve scenario.

Language: Английский