Zachary Seog
Research Mentor(s): Xin Tong
Mentor Department: Molecular & Integrative Physiology
Authors: Zachary Seog, Derrick Jiang , Gary Zhang, Xin Tong
Session: Session 3 (11:00am – 11:50am)
Presentation Type: Poster 60
Abstract
Currently, 30% of the U.S. adult population have metabolic dysfunction-associated steatotic liver disease also known as MASLD or NAFLD. Our lab is interested in the pathways and molecular processes that drive the progression of MASLD. Liver fibrosis, the hallmark of MASLD, is caused by many genetic and molecular pathways. Oxysterol-binding protein-related protein 3 (ORP3) is reported to play a role in lipid transport and is overexpressed in extreme liver fibrosis and hepatocellular carcinoma (HCC). Its precise role in fibrosis generation is not clear. This study aimed to investigate the functional impact of some mutations in human ORP3, like D619E (a missense mutation associated with HCC) and S437P/Y759P (phosphorylation sites), on its profibrogenic activity. We introduced these mutations into ORP3 by site-directed mutagenesis and verified them by sequencing. Transfection of wild-type and mutant ORP3 constructs into human 293 AD cells followed by Western blotting confirmed the expression of the mutants. Early results suggest that ORP3 overexpression initiates profibrogenic gene expression, as indicated by upregulated mRNA and protein expression of the genes Ctgf, Thbs1, and PdgfB. Future studies can include in vivo research to take into account the impact of the mutations on ORP3 function during a murine model of liver fibrosis. Data on the role of ORP3 and ORP3 mutation in fibrogenesis can suggest new therapeutic possibilities for MASLD and HCC.
