University of Massachusetts Medical Center
UMass Medical School
PRMT5s regulation of SREBP1 expression in hepatocytes was investigated in the context of NAFLD. Depleting PRMT5 expression by shRNA mediated gene silencing or inhibiting its enzymatic activity by a small molecule inhibitor decreased SREBP1 expression on mRNA and protein levels. There is no change on its direct target genes involved in de novo lipogenesis. PRMT5 knockdown or inhibition reduced the PI3K-AKT signaling pathway, in which the expression of genes involved in mitochondrial biogenesis was significantly enhanced. As a consequence of PRMT5 inhibition, lipid droplet accumulation was decreased in the presence of a PRMT5 inhibitor. The results indicate that PRMT5 regulates hepatic lipid homeostasis independent of SREBP1 and that PRMT5 inhibitor could have beneficial effects on NAFLD.
Worcester Polytechnic Institute
Major Qualifying Project
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Chemistry and Biochemistry