2021 Fiscal Year Final Research Report
The role of extracellular vesicles in the pathobiology of lymphangioleiomyomatosis
| Project/Area Number |
19K08611
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53030:Respiratory medicine-related
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | リンパ脈管筋腫症 / 細胞外小胞 / リンパ管新生 / mTORシグナル / 形質転換 |
|---|
| Outline of Final Research Achievements |
Chyle leak is a peculiar complication in lymphangioleiomyomatosis (LAM) and therefore must be precious material to elucidate pathobiology of LAM. We examined the exosomes obtained from serum and chylous pleural effusion (CPL) in patients with LAM. When fetal lung fibroblast cell line (HFL-1) were exposed with the exosomes from CPL (CPL-exosomes), we found the expression of NOTCH1 and RHEB mRNAs were upregulated about 1.5-2.0 fold. However, we could not demonstrate this upregulation in protein levels. Microarray analysis of miRNAs in CPL-exosomes revealed that the expression levels of 5 miRNAs (miR-21、miR-23a、miR-23b、miR-26、and miR-451a) were significantly decreased as compared with those in the exosomes from control chylous pleural effusions. However, this was not associated with the miRNAs levels in serum from LAM patients irrespective of during or before sirolimus treatment.
|
| Free Research Field |
呼吸器内科学
|
| Academic Significance and Societal Importance of the Research Achievements |
患者診療により得られる病態解明への示唆や臨床検体を研究に生かし、「TSC変異陽性LAM細胞はEVsを分泌し周辺細胞にphenotype transferして病巣を形成する。このメカニズムを明らかにすれば、病態解明と新規治療の開発につながるのではないか？」という学術的問いを解明する、学術的および社会的意義のある研究である。
|
