Time-course expression profile and diagnostic potential of a miRNA panel in exosomes and total serum in acute liver injury

• Published in: The international journal of biochemistry & cell biology 2018-07, Vol.100, p.11-21
• Main Authors: Motawi, Tarek K., Mohamed, Mohamed R., Shahin, Nancy N., Ali, Mohamed A.M., Azzam, May A.
• Format: Article
• Language: English
• Subjects: Acetaminophen; Biomarkers; Drug-induced liver injury; Extracellular vesicles; Thioacetamide
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2018.05.002

[Display omitted] •Exosomes are stable miRNA reservoirs, yet most studies are performed on serum.•MicroRNA compartmentalization within exosomes or total serum is etiology-dependent.•Exosomal miRNA-122 showed higher diagnostic power & wider diagnostic window in ALI.•Exosomal miRNAs showed earlier & superior diagnostic potential following TAA injury.•Exosomal miRNAs can differentiate between different etiologies of liver injury. Circulating miRNAs have recently emerged as attractive candidates for biomarker discovery. However, they have a variant distribution in circulation, and the diagnostic significance of their compartmentalization is yet to be elucidated. This study explored the time-course expression profile and the diagnostic potential of miRNAs-122a-5p, 192-5p, 193a-3p and 194-5p in exosomal and total serum compartments in two rat models of acute liver injury (ALI)11ALI: acute liver injury; miRNA: micro RNA; DILI: drug induced liver injury; ACAP: acetaminophen; TAA: thioacetamide; TEM: transmission electron microscopy; ROC: Receiver operator characteristic analysis; AUROC: Area under ROC.. Exosomes were isolated and characterized in terms of morphology, size and CD-63 surface marker expression. Exosomal, serum and hepatic miRNAs were quantified using q-RT-PCR. An inverse expression pattern of hepatic and total serum miRNAs was observed following acetaminophen or thioacetamide-induced liver injury. Conversely, exosomal miRNAs expression pattern varied according to the type of injury. Overall, ROC analysis revealed superior discriminatory ability of exosomal miRNA-122a-5p following either acetaminophen or thioacetamide injury with earlier diagnostic potential and a wider diagnostic window compared to the corresponding total serum counterpart. Moreover, exosomal miRNAs showed higher correlation with ALT activity in both models. In conclusion, exosomal miRNA-122a-5p shows higher diagnostic performance with a broader diagnostic time window and an earlier diagnostic potential than its serum counterpart in ALI. Furthermore, exosomal miRNAs-122a-5p, 192-5p and 193a-3p exhibit an injury-specific signature in ALI and can be used not only as diagnostic tools in liver injury but also to differentiate between different etiologies of injury.