2021 Fiscal Year Final Research Report
New mechanism of autophagy inhibition from the study of preeclampsia
| Project/Area Number |
19K09750
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
|
|---|
| Research Institution | University of Toyama |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
島 友子 富山大学, 学術研究部医学系, 助教 (00377285)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | 妊娠高血圧症候群 / オートファジー / TFEB / Atg4B / 合胞体化 |
|---|
| Outline of Final Research Achievements |
The number of women with hypertensive disorders of pregnancy, HDP, will be increased in Japan, in which aging society proceeds rapidly. Therefore, we must tackle this problem to find out a treatment for this disease. This study has been clarified that placental autophagy deficiency is caused of TFEB inactivation and failure of ATG4B functions. In addition, the decrease of serum beta-galactosidase and the increase of aggregated protein were observed in women with HDP, suggesting that they are available for predicting placentas with autophagy failure. International collaborative study also showed that autophagy deficiency in trophoblasts enhanced the occurrence of pyroptosis triggered by endoplasmic reticulum stress. In other words, autophagy might be caused of pathogen-free inflammation in HDP. Taken together with these results, we are going to develop a medicine to activate placental autophagy by modulating TFEB or ATG4B pathway.
|
| Free Research Field |
産科婦人科
|
| Academic Significance and Societal Importance of the Research Achievements |
これまで妊娠高血圧症候群におけるオートファジー研究には体系的な検討がなされておらず、本研究によりその病態の原因の一つが明らかになったことは、今後の治療法へと繋がる可能性がある。
一方で、妊婦への薬剤投与は母体のみならず胎児への影響から開発が難しい領域であるが、胎盤を介して病態を紐解くことで将来的な妊娠中治療へと繋がると考える。更に超高齢化社会日本ではHDPによって未熟児出生率の増加も懸念されることから（成人後の糖尿病や高血圧の増加とも関連）、HDP治療法の開発により早産を減らすことができれば、ひいては新生児の健やかな発育の基本となるものであり、日本社会にポジティブに作用する研究である。
|
