| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2009: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
|
|---|
| Research Abstract |
Adrenal glucocorticoids produce their hormone actions via a signal pathway involving ubiquitously expressed glucocorticoid receptor(GR), a prototypic member of the nuclear receptor superfamily, which acts as a ligand-dependent transcription factor. Upon binding glucocorticoids, GR translocates into the nucleus and binds the glucocorticoid response element(GRE) on the target gene promoters. Binding of liganded receptors with target DNA is followed by recruitment of mediators and coactivators to the proximity of the target DNA, resulting in RNA polymerase II(RNAPII) recruitment nearby transcription start sites and activation of transcription. In skeletal muscle, glucocorticoids elicit a variety of biological actions in metabolism of glucose, lipids, and proteins and contribute to metabolic homeostasis. On the other hand, glucocorticoids are used as a key drug for treatment of, for example, inflammatory disorders, hematologic malignancies, and allergic diseases, and prolonged oversecretion or exogenous administration of glucocorticoid drug gives rise to undesirable effects including muscle atrophy. given this, we decided to explore GR target gene via genome wide approach, especially in skeletal and cardiac muscles
In skeletal muscle, we confirmed that KLF15 and REDD1 are direct target genes of GR, playing important roles in mTOR inhibition and muscle atrophy via distinct pathways. Together with the results with cardiac muscles, we think that our genome wide approach will clarify the biological significance of GC-GR system and contribute to further understanding of human physiology and development of GC therapy.
|
