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- Title
Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD.
- Authors
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
- 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 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.
- Subjects
FATTY liver; EXTRACELLULAR vesicles; NON-alcoholic fatty liver disease; FATTY degeneration; HIGH-carbohydrate diet; HIGH cholesterol diet
- Publication
Liver International, 2023, Vol 43, Issue 9, p1909
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.15604