DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation

iScience

Akiko Kubo¹  Hiroshi Itoh²  Kazutoshi Miyashita²  Kenichiro Kinouchi³  Norifumi Yoshimoto⁴  Ran Nakamichi⁴  Toshiaki Monkawa⁴  Kaori Hayashi⁴  Riki Akashio⁴  Akihito Hishikawa⁴  Akinori Hashiguchi⁴  Erina Sugita⁴  Tatsuhiko Azegami⁴  Makoto Suematsu⁵ 

[1] Corresponding author;Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan;Department of Pathology, Keio University School of Medicine, Tokyo, Japan;Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;Medical Education Center, Keio University School of Medicine, Tokyo, Japan;

关键词: Pathophysiology;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown