文章基本信息

标题：DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation
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作者：Akihito Hishikawa ; Kaori Hayashi ; Akiko Kubo 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：12
页码：1-21
DOI：10.1016/j.isci.2021.103436
语种：English
出版社：Elsevier
摘要：SummaryThe “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.Graphical abstractDisplay OmittedHighlights•KAT5-mediated DNA damage repair acts against ischemia-reperfusion (IR) injuries•K-Cl cotransporter3 (KCC3) expression is decreased in damaged proximal tubular cells•Decreased KCC3 may lead to AKI via acceleration of tubuloglomerular feedback•KAT5 induces KCC3 expression through an epigenetic mechanismPathophysiology; Cell biology