Project/Area Number |
17390023
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
|
Research Institution | Nagoya City University |
Principal Investigator |
IMAGAWA Masayoshi Nagoya City University, Graduate School of Pharmaceutical Sciences, Molecular Biology, Professor (20136823)
|
Co-Investigator(Kenkyū-buntansha) |
NISHIZUKA Makoto Nagoya City University, Graduate School of Pharmaceutical Sciences, Molecular Biology, Research Associate (00363953)
|
Project Period (FY) |
2005 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥16,140,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2007: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2006: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2005: ¥5,100,000 (Direct Cost: ¥5,100,000)
|
Keywords | Obesity / Adipocyte / Diabetes / Differentiation / Transcrintion Factor / Molecular Biology / Biochemistry |
Research Abstract |
Adipocyte differentiation is known to be regulated by a complex array of genes known as master regulators. We previously isolated 102 genes, which are expressed in the early stage of adipocyte differentiation. In this study, we characterized identified genes including fads (factor for adipocyte differentiation), which are unknown genes. 1. The knockdown and over-expression experiments for fad158 revealed that fad158 has the ability to regulate adipocyte differentiation positively, especially at an early stage. 2. The expression level of fad104 quickly increased in the early stage of adipogenesis. FAD104 revealed the possible presence of a fibronectin type III domain and transmembrane domain. We have developed fad104 knockout mice and characterizing now. 3. The knock down of fad24 repressed mitotic clonal expansion (MCE). Moreover, FAD24 interacts with HBO1, a histone acetyltransferase and positive regulator of DNA replication initiation, and acts in concert with HBO1 to promote adipogenes
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is by controlling DNA replication. 4. We also isolated the new gene, fad49. The RNA interference assay revealed that this gene also has some critical roles on adipocyte differentiation. Moreover, fad49 may function as a scaffold protein during adipocyte differentiation. 5. One unknown gene was identified as an imprinted gene, peg (paternally expressed gene) 10. The knockdown of peg10 by RNA interference inhibited the differentiation of 3T3-L1 cells into lipid-laden adipocytes. Interestingly, peg10 RNAi-treatment reduced the expressions of C/EBPβ and C/EBPδ, and inhibited MCE. 6. Cyclin D2 was also identified from unknown genes. The expression of cyclin D1 and cyclin D3, the other D-type cyclins, was also transiently induced early during adipocyte differentiation. Each of the D-type cyclins seems to play a crucial role in adipocyte differentiation by regulating MCE.. Thus, we characterized newly identified genes, whose expression increased rapidly at the early stage of adipocyte differentiation. Some genes have crucial roles in adipogenesis. Less
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