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非受容体型チロシンキナーゼSykの子宮内膜脱落膜化に与える影響の解析

非受体酪氨酸激酶Syk对子宫内膜蜕膜化的影响分析

基本信息

批准号：
23791843
负责人：
陌間亮一
金额：
$ 2.75万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791843/
关键词：
シグナル伝達発生・分化チロシンキナーゼ

项目摘要

研究開始当初の背景:ヒト子宮内膜間質細胞において、mAC特異的阻害剤であるTSA(trichostatin A)が転写に作用した結果、内膜間質細胞の脱落膜化においてIGFBP-1やprolactinなど分化マーカーの亢進を示したとする論文(JBC 2003)がある。核内代謝への影響と帰結しているが、TSAは核内HDACのみならず、細胞質内に存在するHI)AC6も阻害することから、細胞質内のチロシンキナーゼSykとHDACとの関連性を示す論文(Genes to Cells 2009)をもとに、子宮内膜間質細胞の分化への影響を調べる意義はあると思われた。現時点においても、チロシンキナーゼSykの脱落膜化との関連性を指摘する論文は存在しない。研究の目的:生理的現象の解明のみならず、不妊・不育医療における疾患の原因を解明するため、子宮内膜への非受容型チロシンキナーゼSykの発現を証明し、P4-PR刺激に伴う核内での転写の亢進時にピストンのアセチル化・脱アセチル化の修飾のスイッチングにおいて、HDACを介したSykの関与を明らかにする事を目的とした。研究の方法:ヒト正常子宮内膜間質細胞を用いた脱落膜化モデルの培養系確立には、患者へのインフォームドコンセントを得た上でのサンプル採集であり、子宮内膜間質細胞サンプルは、立ち上げとして貴重であった。そのため、事前準備として、抹消血より分離した単球や細胞株(32D等)の培養にて、安定した培養環境の樹立を試みた。研究の成果:開始当初3ヶ月で、培養系の安定を得たが、その直後、細菌感染が培養室内で繰り返し認められ、原因が特定できなかった。続く4ヶ月間は、感染源となる試薬の特定と入れ替えにつとめたが、予算の都合上、総入れ替えを当初は躊躇してしまい、しばらく改善されなかった。試薬総入れ替え、培養室フィルターチェックを含め改善を図ったが、効果がなく、その後、出入りする者の制限と監視、最終的にはインキュベーターも入れ替えた。今年度より改善を得たが、大学病院から他府県への異動を命ぜられ、研究継続が停止した。

At the beginning of the study, the background of the study was as follows: the initial background of the study was as follows: the results of the inhibition of mAC, the inhibition of TSA (trichostatin A), the exfoliative membranization of endometrium, the differentiation of IGFBP-1, the differentiation of prolactin, and the enhancement of JBC 2003. In the nuclei, there are HDAC fragments in the nuclei, TSA in the nuclei, AC6 in the cells, AC6 in the cells, Syk cells in the cells, HDAC genes in the cells, Genes to Cells 2009, cell differentiation in the intima, and differentiation in the inner membrane of the daughter. At the same time, please check that the Syk is falling off and the connection between the two is critical. Objective: to understand the causes of diseases in infertility doctors without pregnancy, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors who do not have pregnancy, to understand the causes of diseases in infertility doctors who do not have pregnancy, to understand the causes of diseases in infertility doctors who do not have pregnancy, to understand the causes of diseases in infertility doctors who do not have pregnancy, to understand the causes of diseases in infertility doctors who do not have pregnancy, to understand the causes of diseases in infertility doctors who do not have pregnancy and infertility, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to find out the causes of diseases in infertility doctors, to understand the causes of diseases in infertility doctors, to understand the HDAC introduces you to Syk and to understand the purpose of the matter. Methods: the culture system of normal fetal endometrium was established by exfoliated membrane culture, and the patient was successfully treated with this method. First, prepare in advance, wipe the blood to separate the cell strain (32D, etc.), culture the cell line, stabilize the environment and set up an environmental test. The results of the study: at the beginning of the first 3 months, the training system received diazepam treatment, and after the first three months, the bacterial infection in the room was returned to the hospital for specific reasons. During the course of 4 months, the source of infection did not register for a specific period of time, closed all the accounts, paid for the purchase for the first time, and made improvements to the health care system. In the training room, there is an increase in the number of people who go in and out of the hospital. In the training room, there is an increase in the number of people who go in and out of the hospital. This year, the quality of the hospital has been improved, the university hospital has asked his government to exercise orders, and the research institute has stopped the program.