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Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-AM-07
Elucidating the Potential Relationship between Metabolic Reprogramming and MicroRNA Behaviors in Activated Hepatic Stellate Cells through Multi-omic Analysis
(1Kyushu Univ., 2AIST)
oTomomi Ichinose1, Seong-Uk Lee1, Yi-Lan Huang1, Daisuke Miura2, Motofumi Kumazoe1, Hirofumi Tachibana1, Yoshinori Fujimura1
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by fibrosis and chronic inflammation. The MASH prevalence continues to increase worldwide; however, yet few effective therapeutic strategies are currently available. To elucidate the detailed mechanisms of the improvement in fibrosis, a comprehensive understanding of the molecules involved in the pathogenesis of MASH is required. Herein, we performed a comprehensive analysis of the transcriptome (mRNA and microRNA (miRNA)) and metabolome to elucidate the potential relationships underlying the molecular behaviors, focusing on the activation of hepatic stellate cells (HSCs), a key initial event in fibrosis. Multi-omic analysis indicated that transforming growth factor-β (TGF-β)-induced activation of HSCs caused metabolic reprogramming represented by enhanced glycolysis, accompanied by changes in amino acid and purine metabolism. Furthermore, we showed that specific miRNAs may regulate both TGF-β signaling and central carbon metabolism in HSC activation. This study demonstrated a new holistic interrelationship among different hierarchical groups of molecules observed in activated HSCs, and deepened the understanding of activated HSC status on the basis of the behaviors of multiple pathway-related molecules, except for common liver fibrosis markers, such as COL1A1 and Acta2. These findings will contribute to the development of biomarkers for the anti-MASH evaluation of drugs, nutraceuticals, and food factors.