2020 Fiscal Year Final Research Report
Significance of hepatic stellate cell trasformation in liver cancer.
| Project/Area Number |
18K07952
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53010:Gastroenterology-related
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
松原 勤 大阪市立大学, 大学院医学研究科, 准教授 (20628698)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | 活性化肝星細胞 / サイトグロビン / 線維化 / 非アルコール性脂肪性肝炎 / TGF-β |
|---|
| Outline of Final Research Achievements |
Liver fibrosis is an intractable disease that, if left untreated, progresses to cirrhosis, of which 2-8% develop liver cancer. Cytoglobin (CYGB) is a protein that is expressed only in hepatic stellate cells (HSC) in the liver and has gas-binding ability. Interestingly, CYGB deficiency in HSC causes fibrosis and carcinogenesis. However, the physiological action and regulation of CYGB expression in activated HSC were unknown. In this study, we found the level of CYGB decreased with the progress of liver fibrosis. TGF-β, an HSC activation inducer, suppressed the expression of CYGB via the pSMAD2/SP3-M1 pathway. In addition, patients with low CYGB expression were found to have increased oxidative DNA damage, demonstrating that CYGB has a role in protecting cells from DNA damage caused by oxidative stress.
|
| Free Research Field |
分子生物学、肝臓学
|
| Academic Significance and Societal Importance of the Research Achievements |
近年、生活習慣の西欧化に伴い肥満や糖尿病と関連する非アルコール性脂肪肝炎（NASH）は増加しており、本邦でも100万人に達する。慢性肝炎は肝線維化を誘発し、多くは不顕性に、且つ、緩徐に進行して肝硬変や肝がんを呈した末期状態で発見される。病因の如何によらず肝がんの母地は肝硬変であることが殆どである。そのため、肝線維化の病態進展を理解し、その原因細胞と考えられる活性化肝星細胞を標的とした新たな治療薬の開発が急務である。本研究では、このHSC特異的に発現するCYGBの発現制御機構を明らかにし、分子基盤に基づいた抗線維化および抗肝がん治療法の開発に繋げる。
|
