DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation.
DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation.
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DOI：
10.1016/j.isci.2021.103436
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发表时间：
2021-12-17
期刊：
影响因子：
5.8
通讯作者：
Itoh H
中科院分区：
文献类型：
--
作者：
Hishikawa A;Hayashi K;Kubo A;Miyashita K;Hashiguchi A;Kinouchi K;Yoshimoto N;Nakamichi R;Akashio R;Sugita E;Azegami T;Monkawa T;Suematsu M;Itoh H
AKI中的"预处理效应"是一种缺血-再灌注事件导致对随后的缺血-再灌注损伤的耐受的现象。但其与DNA损伤修复的关系尚未阐明。在这里，我们展示了KAT5在预处理效应中的作用。预处理减弱了KAT5表达升高的近端肾小管细胞的DNA损伤。近端肾小管细胞特异性KAT5基因敲除小鼠缺血再灌注损伤加重，预处理效应消失。通过MALDI-IMS和尿腺苷对肾小管肾小球反馈（TGF）的研究表明，预处理至少部分通过KAT5引起TGF减弱。此外，K-Cl协同转运蛋白3（KCC3）的表达下降，在受损的近端肾小管细胞，这可能参与加速TGF后IR。此外，KAT5诱导KCC3的表达，通过维持染色质的可及性和结合到KCC3启动子。这些结果表明，一种新的预处理机制介导的促进DNA修复和衰减的TGF-β通过KAT5。KAT5介导的DNA损伤修复作用于缺血-再灌注（IR）损伤K-Cl协同转运蛋白3（KCC 3）表达在受损的近端肾小管细胞中降低KCC 3降低可能通过加速肾小管肾小球反馈导致AKI KAT5通过表观遗传机制诱导KCC 3表达病理生理学;细胞生物学
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. 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 mechanism Pathophysiology; Cell biology
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影响因子：
64.5
作者：
Chaki M;Airik R;Ghosh AK;Giles RH;Chen R;Slaats GG;Wang H;Hurd TW;Zhou W;Cluckey A;Gee HY;Ramaswami G;Hong CJ;Hamilton BA;Cervenka I;Ganji RS;Bryja V;Arts HH;van Reeuwijk J;Oud MM;Letteboer SJ;Roepman R;Husson H;Ibraghimov-Beskrovnaya O;Yasunaga T;Walz G;Eley L;Sayer JA;Schermer B;Liebau MC;Benzing T;Le Corre S;Drummond I;Janssen S;Allen SJ;Natarajan S;O'Toole JF;Attanasio M;Saunier S;Antignac C;Koenekoop RK;Ren H;Lopez I;Nayir A;Stoetzel C;Dollfus H;Massoudi R;Gleeson JG;Andreoli SP;Doherty DG;Lindstrad A;Golzio C;Katsanis N;Pape L;Abboud EB;Al-Rajhi AA;Lewis RA;Omran H;Lee EY;Wang S;Sekiguchi JM;Saunders R;Johnson CA;Garner E;Vanselow K;Andersen JS;Shlomai J;Nurnberg G;Nurnberg P;Levy S;Smogorzewska A;Otto EA;Hildebrandt F
通讯作者：
Hildebrandt F
DNA甲基化介导了1型糖尿病中HBA1C相关并发症的发展。
影响因子：
20.8
作者：
Chen Z;Miao F;Braffett BH;Lachin JM;Zhang L;Wu X;Roshandel D;Carless M;Li XA;Tompkins JD;Kaddis JS;Riggs AD;Paterson AD;DCCT/EDIC Study Group;Natarajan R
通讯作者：
Natarajan R
影响因子：
5.8
作者：
Basile DP;Anderson MD;Sutton TA
通讯作者：
Sutton TA
影响因子：
16
作者：
Choi, Hyo Jei Claudia;Lin, Jia-Ren;Vannier, Jean-Baptiste;Slaats, Gisela G.;Kile, Andrew C.;Paulsen, Renee D.;Manning, Danielle K.;Beier, David R.;Giles, Rachel H.;Boulton, Simon J.;Cimprich, Karlene A.
通讯作者：
Cimprich, Karlene A.
DOI：
10.1053/j.ajkd.2008.11.034
发表时间：
2009-06
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Coca SG;Yusuf B;Shlipak MG;Garg AX;Parikh CR
通讯作者：
Parikh CR