Background: Alcoholic Hepatitis (AH) is the most severe form of Alcoholic Liver Disease (ALD) and current therapies are not fully effective. Targeted therapies are urgently needed. AKR1B10 was recently shown to be overexpressed in patients with AH.
Objectives: To analyze the expression of AKR1B10, an aldose reductase, through a translational approach in order to better understand the potential for aldose reductase as a novel target of therapy in AH.
Methods: RNA was extracted from human tissue samples from patients with various liver diseases, animal models of fibrosis and alcoholic liver disease, and cultured Hepatic Stellate Cell (HSC) lines stimulated with proinflammatory, profibrogenic, and AKR1B10 treatments, and the samples were quantified using qPCR analysis.
Results: Human samples showed nearly a 100-fold increase of AKR1B10 expression in patients with AH. An animal model of liver fibrosis showed a small increase in Akr1b8 (AKR1B10 mouse analogue) expression. HSCs did not show any noticeable increase in expression of AKR1B10 regardless of treatment, and did not show any noticeable increase in expression of proinflammatory or profibrogenic genes when treated with AKR1B10.
Conclusion: The increased expression of AKR1B10 and its mouse analogue, while present in patients with AH and fibrotic mice, respectively, may not be mediated by HSCs. Further studies are needed to better understand location and nature of overexpression.Bachelor of Science in Public Healt
