Investigation of the relationship between ploidy alterations and senescence of hepatocytes in liver injuries

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15974
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka University
• Principal Investigator: Matsumoto Tomonori 大阪大学, 微生物病研究所, 助教 (40886610)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 多倍体 / 細胞老化 / DNA傷害 / 細胞障害

Outline of Final Research Achievements

In this study, we focused on two cellular changes, polyploidization and cell senescence, which accumulate with aging and organ damage, and aimed to elucidate their relationship. Using the human hepatoma cell line Huh7 and the normal diploid epithelial cell line RPE1, we found that the process of cellular senescence induction was often accompanied by polyploidization, but that polyploidization was not essential for cellular senescence. Using stably polyploid cell lines, we also revealed that high levels of DNA damage were accumulated in polyploid cells, and that polyploidization could induce DNA damage. Our results suggest that polyploidization and polyploidy are not essential for induction of cellular senescence but are closely related to the induction of cellular senescence in association with the accumulation of DNA damage.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

加齢や臓器障害において多倍体化と細胞老化という2つの細胞変化がともに亢進・蓄積しており、特に細胞老化は様々な加齢性疾患の病態に関与していることがこれまで明らかとなってきているが、特に多倍体化の意義についてはほとんど明らかとなっていない。本研究により多倍体化と細胞老化惹起との相互連関が明らかになったことにより、未だ謎が多い、細胞障害における多倍体化が持つ意義の一側面が解明された。今後さらに検討を進めることで、臓器障害における多倍体化の意義の解明にもつながることが期待される。