Extracellular vesicles in hepatology: Physiological role, involvement in pathogenesis, and therapeutic opportunities

Azparren‐Angulo, M.; Royo, Félix; González, Esperanza; Liebana, Marc; Brotons, Bruno; Berganza, J.; Goñi‐de‐Cerio, Felipe; Manicardi, Nicoló; Abad-Jordà, Laia; Gracia‐Sancho, Jordi; Falcón‐Pérez, Juan Manuel

doi:10.1016/j.pharmthera.2020.107683

Cited by 27 publications

(24 citation statements)

References 201 publications

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“…21,22 EVs and their contents have been reported to be the potential biomarkers for the diagnosis and prognosis of diseases including ALD. 14,23,24 Previous study has shown that alcohol exposure could release CD40L-containing EVs from hepatocytes, which stimulated the activation of macrophages and led to inflammation in ALD. 14 However, the correlation between EVs and ALD progression still needs to be further investigated.…”

Section: Introductionmentioning

confidence: 99%

DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD

Tan

Zhang

Wang

et al. 2022

Molecular Therapy - Nucleic Acids

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DNA damage-regulated autophagy modulator 1 (DRAM1) could play important roles in inflammation and hepatic apoptosis, while its roles in alcohol-related liver disease (ALD), which is characterized by hepatic inflammation and apoptosis, are still unclear. In this study, we explored the expression, role, and mechanism of DRAM1 in ALD. Firstly, our results showed that DRAM1 was significantly increased in liver tissues of mice at the early stage of alcohol treatment. In addition, DRAM1 knockout reduced, and liver-specific overexpression of DRAM1 aggravated, alcohol-induced hepatic steatosis, injury, and expressions of M1 macrophage markers in mice. Furthermore, ethanol-induced DRAM1 of hepatic cells increased pyruvate kinase M2 (PKM2)-enriched extracellular vesicles (EVs), and ectosomes derived from hepatic cells with DRAM1 overexpression promoted macrophage activation. Mechanistic investigations showed that DRAM1 interacted with PKM2 and increased the PKM2 level in plasma membrane. At last, DRAM1 was significantly increased in liver tissues of ALD patients, and it was positively correlated with M1 macrophage markers. Taken together, this study revealed that ethanol-induced DRAM1 of hepatic cells could increase the PKM2-enriched EVs, promote macrophage activation, and aggravate the disease progression of ALD. These findings suggested that DRAM1 might be a potentially promising target for the therapy of ALD.

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Section: Introductionmentioning

confidence: 99%

DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD

Tan

Zhang

Wang

et al. 2022

Molecular Therapy - Nucleic Acids

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“…Serum and plasma EVs have been largely studied as sources of biomarkers and hepatic conditions are not the exception 30 , 31 . Indeed, they also contribute to the function in liver 26 . However, in chronic patients, blood sampling becomes more problematic as the illness worsens.…”

Section: Discussionmentioning

confidence: 99%

“…As EVs are secreted by all cell studied so far and can reach not only the cell environment but also different body fluids, they are being studied as sources of new biomarkers in a wide range of diseases 23 , 24 . Liver diseases are not the exception, the involvement of EVs in physiological and pathogenic processes hold by the liver have been extensively demonstrated 25 , 26 and consequently, their study as biomarkers sources for diagnosis and monitoring of hepatic conditions is granted 27 - 29 .…”

Section: Introductionmentioning

confidence: 99%

Could protein content of Urinary Extracellular Vesicles be useful to detect Cirrhosis in Alcoholic Liver Disease?

et al. 2021

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Alcohol abuse has a high impact on the mortality and morbidity related to a great number of diseases and is responsible for the development of alcoholic liver disease (ALD). It remains challenging to detect and evaluate its severity, which is crucial for prognosis. In this work, we studied if urinary EVs (uEVs) could serve in diagnose and evaluate cirrhosis in ALD. To this purpose, uEVs characterization by cryo-electron microscopy (Cryo-EM), Nanoparticle Tracking Analysis (NTA) and Western blotting (WB) was performed in a cohort of 21 controls and 21 cirrhotic patients. Then, proteomics of uEVs was carried out in a second cohort of 6 controls and 8 patients in order to identify new putative biomarkers for cirrhosis in ALD. Interestingly, uEVs concentration, size and protein composition were altered in cirrhotic patients. From a total of 1304 proteins identified in uEVs, 90 of them were found to be altered in cirrhotic patients. The results suggest that uEVs could be considered as a tool and a supplier of new biomarkers for cirrhosis in ALD, whose application would be especially relevant in chronic patients. Yet, further research is necessary to obtain more relevant result in clinical terms.

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“…Serum and plasma EVs have been largely studied as sources of biomarkers and hepatic conditions are not the exception [56,57]. Indeed, they also contribute to the function in liver [26]. However, in chronic patients, blood sampling becomes more problematic as the illness worsens.…”

Section: Discussionmentioning

confidence: 99%

“…As EVs are secreted by all cell studied so far and can reach not only the cell environment but also different body fluids, they are being studied as sources of new biomarkers in a wide range of diseases [23,24]. Liver diseases are not the exception, the involvement of EVs in physiological and pathogenic processes hold by the liver have been extensively demonstrated [25,26] and consequently, their study as biomarkers sources for diagnosis and monitoring of hepatic conditions is granted [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Could Protein Content of Urinary Extracellular Vesicles be Useful to Detect Alcoholic Liver Disease and Assess Hepatocarcinoma Risk?

F¹

2021

Preprint

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(1) Background: Alcohol abuse has a high impact on the mortality and morbidity related to a great number of diseases and is responsible for the development of alcoholic liver disease (ALD). It remains challenging to detect and evaluate its severity, which is crucial for prognosis. In this work, we studied if urinary EVs (uEVs) could serve in diagnose and evaluate cirrhosis in ALD. (2) Methods: uEVs characterization by cryo-electron microscopy (Cryo-EM), Nanoparticle Tracking Analysis (NTA) and Western blotting (WB) was performed in a cohort of 21 controls and 21 cirrhotic patients. Then, proteomics of urinary EVs (uEVs) was carried out in a second cohort of 6 controls and 8 patients in order to identify new putative biomarkers for cirrhosis in ALD. (3) Results: uEVs concentration, size and composition were altered in cirrhotic patients. A total of 1304 proteins were identified in uEVs, and 90 of them were found to be altered in cirrhotic patients. (4) Conclusions: uEVs could be considered as a tool and a supplier of new biomarkers for ALD, whose application would be especially relevant in chronic patients. Yet, further research is necessary to obtain more relevant result in clinical terms.

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Extracellular vesicles in hepatology: Physiological role, involvement in pathogenesis, and therapeutic opportunities

Cited by 27 publications

References 201 publications

DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD

DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD

Could protein content of Urinary Extracellular Vesicles be useful to detect Cirrhosis in Alcoholic Liver Disease?

Could Protein Content of Urinary Extracellular Vesicles be Useful to Detect Alcoholic Liver Disease and Assess Hepatocarcinoma Risk?

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