2022 Fiscal Year Final Research Report
Mechanism for the roles of cholesterol-binding membrane protein TSPO2 in terminal erythroid differentiation
| Project/Area Number |
20H03138
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 42020:Veterinary medical science-related
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
Inaba Mutsumi 北海道大学, 獣医学研究院, 教授 (00183179)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
高田 健介 北海道大学, 獣医学研究院, 准教授 (40570073)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | 赤芽球造血 / 赤血球 / 赤芽球 / コレステロール / コレステロール結合蛋白質 / 貧血 |
|---|
| Outline of Final Research Achievements |
The roles of TSPO2, a transmembrane cholesterol-binding protein expressed in late erythroblasts, were examined using Tspo2 knockout mouse models. Bone marrow-derived TSPO2-deficient erythroid cells, as well as Tspo2-knockout MEDEP cells, showed impaired cytokinesis and morphological defects associated with a cell-cycle arrest, resulting in decreased cell proliferation and delays in erythroid maturation with a consequent reduction in red cell production. TSPO2-deficient erythroid cells exhibited an increased release of incorporated cholesterol. The expression of HA-tagged TSPO2 that found in the Golgi apparatus and lysosomes, by transient expression and gene editing, rescued such defects, whereas the supplementation of exogenous cholesterol had no effect. These findings imply that TSPO2 is essential for coordination of maturation and proliferation of erythroblasts during normal erythropoiesis and that TSPO2 regulates intracellular distribution of cholesterol in late erythroblasts.
|
| Free Research Field |
獣医学、生化学、血液学
|
| Academic Significance and Societal Importance of the Research Achievements |
近年、貧血患者における低コレステロール血症やコレステロール過剰と赤血球産生異常の関係など、赤芽球系造血におけるコレステロール代謝の重要性が報告されているが、赤血球産生過程でコレステロールがどのように関わるのか、その機作や実態は不明である。本研究成果は、TSPO2という膜タンパク質が赤芽球の細胞内コレステロールを制御して赤芽球系終末分化における生理的な細胞増殖と成熟を支え、効率的な赤血球生産を可能にすることを示したものであり、生理的赤血球産生機序の解明、貧血等疾患の的確な診断・治療、人口赤血球産生の効率化、さらにコレステロールに関する適正な医療情報等に大きな学術的・社会的意義を有する。
|
