DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation
Summary: The “preconditioning effect” in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221014073 |
| _version_ | 1819174654408916992 |
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| author | Akihito Hishikawa Kaori Hayashi Akiko Kubo Kazutoshi Miyashita Akinori Hashiguchi Kenichiro Kinouchi Norifumi Yoshimoto Ran Nakamichi Riki Akashio Erina Sugita Tatsuhiko Azegami Toshiaki Monkawa Makoto Suematsu Hiroshi Itoh |
| author_facet | Akihito Hishikawa Kaori Hayashi Akiko Kubo Kazutoshi Miyashita Akinori Hashiguchi Kenichiro Kinouchi Norifumi Yoshimoto Ran Nakamichi Riki Akashio Erina Sugita Tatsuhiko Azegami Toshiaki Monkawa Makoto Suematsu Hiroshi Itoh |
| author_sort | Akihito Hishikawa |
| collection | DOAJ |
| description | Summary: The “preconditioning effect” in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5. |
| first_indexed | 2024-12-22T20:42:24Z |
| format | Article |
| id | doaj.art-b9104add2d57440785cf3e54283a323b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-22T20:42:24Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b9104add2d57440785cf3e54283a323b2022-12-21T18:13:18ZengElsevieriScience2589-00422021-12-012412103436DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulationAkihito Hishikawa0Kaori Hayashi1Akiko Kubo2Kazutoshi Miyashita3Akinori Hashiguchi4Kenichiro Kinouchi5Norifumi Yoshimoto6Ran Nakamichi7Riki Akashio8Erina Sugita9Tatsuhiko Azegami10Toshiaki Monkawa11Makoto Suematsu12Hiroshi Itoh13Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding authorDepartment of Biochemistry, Keio University School of Medicine, Tokyo, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Pathology, Keio University School of Medicine, Tokyo, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanMedical Education Center, Keio University School of Medicine, Tokyo, JapanDepartment of Biochemistry, Keio University School of Medicine, Tokyo, JapanDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanSummary: The “preconditioning effect” in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5.http://www.sciencedirect.com/science/article/pii/S2589004221014073PathophysiologyCell biology |
| spellingShingle | Akihito Hishikawa Kaori Hayashi Akiko Kubo Kazutoshi Miyashita Akinori Hashiguchi Kenichiro Kinouchi Norifumi Yoshimoto Ran Nakamichi Riki Akashio Erina Sugita Tatsuhiko Azegami Toshiaki Monkawa Makoto Suematsu Hiroshi Itoh DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation iScience Pathophysiology Cell biology |
| title | DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation |
| title_full | DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation |
| title_fullStr | DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation |
| title_full_unstemmed | DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation |
| title_short | DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation |
| title_sort | dna repair factor kat5 prevents ischemic acute kidney injury through glomerular filtration regulation |
| topic | Pathophysiology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221014073 |
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