Elucidation of the mechanism of peritoneal fibrosis via senescence of peritoneal mesothelial cells by histone modification

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17284
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Hiroshima University
• Principal Investigator: Maeda Kazuya 広島大学, 病院(医), 専門研究員 (60832540)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: peritoneal fibrosis

Outline of Final Research Achievements

Peritoneal dialysis is a clinically effective treatment for end-stage renal disease. However, long-term continuation of peritoneal dialysis is challenging due to the decline in peritoneal function caused by peritoneal fibrosis. Exposure to glucose in the dialysis solution can induce stress-induced aging of peritoneal mesothelial cells, contributing to peritoneal fibrosis. Therefore, by protecting peritoneal mesothelial cells, it may be possible to prevent fibrosis and enable long-term continuation of peritoneal dialysis.

In this study, we focused on P16, which is involved in cellular aging, and demonstrated that enhanced transcriptional activity of P16 through histone methylation induces aging of peritoneal mesothelial cells and progresses peritoneal fibrosis. It was revealed that inhibiting this process can suppress peritoneal fibrosis.

Free Research Field

Nephrology

Academic Significance and Societal Importance of the Research Achievements

本研究によってストレス誘導性の腹膜中皮細胞の老化を介した腹膜線維化の機序やその阻害薬によって腹膜線維化を抑制できることが明らかできた。今後将来的に臨床応用することで、これまでよりも腹膜透析の長期継続が可能になること、ひいては更なる普及率の向上に寄与することが期待される。腹膜透析の長期継続によって、患者のQuality of Lifeの維持が期待されるだけではなく、今後さらに高齢社会が進む中で、在宅療法を推進する社会的なニーズに応えるものと思われる。