Novel mechanism of NASH progression mediated by ceramide-enriched exosomes

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17497
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagasaki University
• Principal Investigator: Fukushima Masanori 長崎大学, 病院(医学系), 助教 (80835596)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: NASH / 細胞外小胞

Outline of Final Research Achievements

In this study, we demonstrated that hepatocyte-derived extracellular vesicle secretion, which contributes to the pathogenesis of NASH, is increased when hepatocytes are treated with both lipotoxicity, which causes NASH, and LPS, which is an effect of intestinal bacteria. Although it is generally believed that multiple factors influence the pathological progression of NASH, this study suggests that the presence of LPS together with intestinal bacteria may promote the progression of NASH pathology in terms of extracellular vesicles, rather than the effect of fat toxicity alone.

Free Research Field

NASH

Academic Significance and Societal Importance of the Research Achievements

脂肪毒性と腸内細菌由来のLPSが細胞外小胞の分泌増加に関与していることが証明され、NASHの病態に細胞外小胞が重要な役割を果たしている可能性が示唆された。したがってこの細胞外小胞のさらなる解析が、NASH進展メカニズムを解明する新たな手段となりうる。将来的にはNASH進展予防や治療のターゲット分子として細胞外小胞が重要な役割を果たす可能性があるのではないかと考えている。