Assessment of exosomal biomarkers as potential diagnostics for experimentally induced liver injury / May Azzam Kamelc ; Supervised Tarek Kamal Motawi , Mohamed Ragaa Mohamed , Nancy Nabil Shahin

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

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). 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

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