Article
Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD
Author/s | Muñoz Hernández, Rocío
Gato, Sheila Gil-Gomez, Antonio Aller, Rocio Rojas, Angela Moran, Laura Ampuero Herrojo, Javier Romero Gómez, Manuel |
Department | Universidad de Sevilla. Departamento de Medicina |
Publication Date | 2023 |
Deposit Date | 2024-06-25 |
Published in |
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Abstract | Background and Aims
Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition ... Background and Aims Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. Methods EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy-proven NAFLD patients. Results Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy-proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. Conclusions Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non-invasive biomarker for the evaluation and management of these patients. |
Funding agencies | Consejeria de Economia, Conocimiento, Empresas y Universidad, Junta de Andalucia Consejeria de salud y Familia Instituto de Salud Carlos III Junta de Andalucia Sociedad Andaluza de patologia Digestiva |
Citation | Muñoz Hernández, R., Gato, S., Gil-Gomez, A., Aller, R., Rojas, A., Moran, L.,...,Romero Gómez, M. (2023). Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD. Liver International, 43 (9), 1909-1919. https://doi.org/10.1111/liv.15604. |
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