| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Outline of Final Research Achievements |
NASH is a chronic hepatic inflammation associated with immune cell infiltration and fibrosis. We recently found that mice deficient in PDLIM2, a nuclear ubiquitin E3 ligase containing PDZ and LIM domains, spontaneously develop NASH-like pathology. Notably, PDLIM2-deficient mice develop NASH in the animal facility of Harvard University, but not in RIKEN facility. Since systemic inflammation can be modified by gut microbiota, we colonized gut microbiota of mice form Taconic Farms into germ-free PDLIM2-deficient mice, and found that PDLIM2-deficient mice with Taconic microbiota environment could develop NASH when we fed a normal chow or higher fat diet (9-15% fat). Microarray analysis of Kupffer cells in PDLIM2-deficient liver showed the upregulation inflammation and metabolism-related genes, which contribute to the NASH phenotype. These data suggest that Taconic microbiota or microbiota-derived metabolites are essential for the development of NASH in combination with PDLIM2-deficiency.
|
