Artículo
Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis
Pirola, Carlos Jose
; Fernandez Gianotti, Tomas
; Castaño, Gustavo Osvaldo; Mallardi, Pablo; San Martino, Julio; González López Ledesma, María Mora
; Flichman, Diego Martin
; Mirshahi, Faridodin; Sanyal, Arun J.; Sookoian, Silvia Cristina
Fecha de publicación:
06/2014
Editorial:
B M J Publishing Group
Revista:
Gut - An International Journal Of Gastroenteorology And Hepatology
ISSN:
0017-5749
e-ISSN:
1468-3288
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
OBJECTIVES: We used a screening strategy of global serum microRNA (miRNA) profiling, followed by a second stage of independent replication and exploration of liver expression of selected miRNAs to study: (1) the circulating miRNA signature associated with non-alcoholic fatty liver disease (NAFLD) progression and predictive power, (2) the role of miRNAs in disease biology and (3) the association between circulating miRNAs and features of the metabolic syndrome. METHODS: The study used a case-control design and included patients with NAFLD proven through biopsy and healthy controls. RESULTS: Among 84 circulating miRNAs analysed, miR-122, miR-192, miR-19a and miR-19b, miR-125b, and miR-375 were upregulated >2-fold (p<0.05) either in simple steatosis (SS) or non-alcoholic steatohepatitis (NASH). The most dramatic and significant fold changes were observed in the serum levels of miR-122 (7.2-fold change in NASH vs controls and 3.1-fold change in NASH vs SS) and miR-192 (4.4-fold change in NASH vs controls); these results were replicated in the validation set. The majority of serum miR-122 circulate in argonaute2-free forms. Circulating miR-19a/b and miR-125b were correlated with biomarkers of atherosclerosis. Liver miR-122 expression was 10-fold (p<0.03) downregulated in NASH compared with SS and was preferentially expressed at the edge of lipid-laden hepatocytes. In vitro exploration showed that overexpression of miR-122 enhances alanine aminotransferase activity. CONCLUSIONS: miR-122 plays a role of physiological significance in the biology of NAFLD; circulating miRNAs mirror the histological and molecular events occurring in the liver. NAFLD has a distinguishing circulating miRNA profile associated with a global dysmetabolic disease state and cardiovascular risk.
Palabras clave:
Fatty Liver Disease
,
Nonalcoholic Steatohepatitis
,
Liver
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IDIM)
Articulos de INST.DE INVEST.MEDICAS
Articulos de INST.DE INVEST.MEDICAS
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Pirola, Carlos Jose; Fernandez Gianotti, Tomas; Castaño, Gustavo Osvaldo; Mallardi, Pablo; San Martino, Julio; et al.; Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis; B M J Publishing Group; Gut - An International Journal Of Gastroenteorology And Hepatology; 64; 5; 6-2014; 800-812
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