2018 Fiscal Year Annual Research Report
Interaction between cell membrane and nuclear hormone receptor in brain development and its modification by environmental chemicals
| Project/Area Number |
18J23449
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| Research Institution | Gunma University |
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Principal Investigator |
アリヤニ ウィンダ 群馬大学, 大学院医学系研究科, 特別研究員(DC1)
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| Project Period (FY) |
2018-04-25 – 2021-03-31
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| Keywords | Thyroid hormone / non-genomic / migration / proliferation / integrin |
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| Outline of Annual Research Achievements |
Thyroid hormones (THs) are known can bind to integrin αVβ3 and induces non-genomic pathway that involved on cell proliferation and migration. The purpose of this study is to investigate non-genomic effects of THs during cell proliferation and migration. I found that TH derivate (T3, T4, rT3, Triac and Tetrac) induced cell proliferation and migration in astrocyte cells, these effects were suppressed by cyclo-RGD (an integrin αVβ3 inhibitor). THs derivate also induced the phosphorylation of ERK1/2, Akt, and mTOR. THs also activate F-actin activity and cortical F-actin score index. This results indicate that the effect was mediated through integrin αVβ3 pathway, at least in part. In addition, I also examined the effects of environmental chemicals such as gadolinium (gadolinium-based contrast agents) on cell proliferation and migration in C6, glioma and Neuro-2A, neuroblastoma cell line. I also examined the effects of soybean isoflavone (genistein, daidzein, and S-Equol) on cerebellar development by primary cerebellar culture of Purkinje cells through the thyroid hormone receptor action. Now I also have one manuscript in preparation about the effects of S-Equol on cerebellar development.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
This this project was runs according to the deadline of the proposal. I have completed all the basic physiological experiments about the non-genomics effects of thyroid hormones on the cell proliferation and migration. Next I will continue to investigate the mechanism of thyroid hormone induced cell migration through the F-actin modulation.
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| Strategy for Future Research Activity |
This year I plan to clarify the mechanism thyroid hormone-induced cell migration through the F-actin modulation. I planned to examined the short exposure of thyroid hormone on cell migration and also examined the effects after knockdown of thyroid hormone receptor. Next I will continue to find the mechanism by measure the protein expression level with western blot for Rho-GTPase cascade including RhoA, RhoB, RhoC, Rac1/2/3, and cdc42 to clarify the modulation of F-actin by thyroid hormone.
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