Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.

Autor:	Muñoz‐Hernández, Rocío, Gato, Sheila, Gil‐Gómez, Antonio, Aller, Rocío, Rojas, Angela, Morán, Laura, Gallego, Javier, Blázquez‐López, Elena, Gallego‐Durán, Rocío, Montero‐Vallejo, Rocío, García‐Fernández, Vanessa, Maya‐Miles, Douglas, Rico, María del C, Cubero, Francisco J, Vaquero, Javier, Ampuero, Javier, Bañares, Rafael, Romero‐Gómez, Manuel
Předmět:	FATTY liver EXTRACELLULAR vesicles NON-alcoholic fatty liver disease FATTY degeneration HIGH-carbohydrate diet HIGH cholesterol diet
Zdroj:	Liver International; Sep2023, Vol. 43 Issue 9, p1909-1919, 11p, 1 Chart, 4 Graphs
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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