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Updated: Jan 30, 2026
Methylated DNA Immunoprecipitation
Published on: January 2, 2009
Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes
Akihito Hishikawa1, Kaori Hayashi1, Takaya Abe2
1Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Abstract:
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.
Insights
Kidney podocyte damage repair via KAT5 is crucial for maintaining kidney health and DNA methylation. Decreased KAT5 leads to kidney disease, but its restoration can improve outcomes.
Area of Science:
- Nephrology
- Molecular Biology
- Epigenetics
Background:
- Altered DNA methylation is implicated in kidney disease progression.
- The mechanisms underlying these epigenetic changes in kidney disease remain unclear.
Purpose of the Study:
- To investigate the role of KAT5-mediated DNA damage repair in kidney podocyte maintenance.
- To explore the association between KAT5, DNA damage, and DNA methylation in kidney disease.
Main Methods:
- Utilized podocyte-specific KAT5-knockout mouse models.
- Analyzed DNA double-strand breaks (DSBs), DNA methylation status, and nephrin expression.
- Investigated KAT5 function in diabetic nephropathy models and employed gene transfer for KAT5 restoration.
Main Results:
- Podocyte-specific KAT5 knockout led to severe albuminuria, increased DSBs, nephrin promoter hypermethylation, and reduced nephrin expression.
- Diabetic nephropathy showed decreased podocyte KAT5, elevated DSBs, and increased DNA methylation.
- KAT5 restoration attenuated albuminuria and reduced DSBs and DNA methylation at the nephrin promoter.
Conclusions:
- KAT5-mediated DNA damage repair is essential for podocyte function and kidney health.
- Decreased KAT5 activity contributes to kidney disease by increasing DNA damage and aberrant DNA methylation.
- Targeting KAT5 may offer a therapeutic strategy for kidney diseases associated with DNA damage and epigenetic alterations.
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