Journal
CELL REPORTS
Volume 26, Issue 5, Pages 1318-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.01.005
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [25860687, 16K19496]
- Keio University Research Grants for Life Science and Medicine
- Banyu Life Science Foundation International
- Ishibashi Yukiko Memorial Foundation
- Japan Medical Woman's Association
- Japanese Association of Dialysis Physicians
- Asahi Life Foundation
- Takeda Science Foundation
- Daiwa Securities Health Foundation in Tokyo, Japan
- Keio University [201813428]
- Grants-in-Aid for Scientific Research [25860687, 16K19496] Funding Source: KAKEN
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Altered DNA methylation plays an important role in the onset and progression of kidney disease. However, little is known about how the changes arise in disease states. Here, we report that KAT5-mediated DNA damage repair is essential for the maintenance of kidney podocytes and is associated with DNA methylation status. Podocyte-specific KAT5-knockout mice develop severe albuminuria with increased DNA double-strand breaks (DSBs), increased DNA methylation of the nephrin promoter region, and decreased nephrin expression. Podocyte KAT5 expression is decreased, whereas DNA DSBs and DNA methylation are increased in diabetic nephropathy; moreover, KAT5 restoration by gene transfer attenuates albuminuria. Furthermore, KAT5 decreases DNA DSBs and DNA methylation at the same nephrin promoter region, which indicates that KAT5-mediated DNA repair may be related to DNA methylation status. These results suggest a concept in which an environment of DNA damage repair, which occurs with decreased KAT5, may affect DNA methylation status.
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