Characterization of ferroptosis in kidney tubular cell death under diabetic conditions.
Characterization of ferroptosis in kidney tubular cell death under diabetic conditions.
复制标题
糖尿病条件下肾小管细胞死亡中铁凋亡的特征。
DOI：
10.1038/s41419-021-03452-x
复制
发表时间：
2021-02-08
影响因子：
9
通讯作者：
Park JT
中科院分区：
文献类型：
--
作者：
Kim S;Kang SW;Joo J;Han SH;Shin H;Nam BY;Park J;Yoo TH;Kim G;Lee P;Park JT
已知转化生长因子-β1 （TGF-β1）诱导的肾小管细胞死亡可导致糖尿病肾病，这是糖尿病的主要并发症。caspase- 3依赖性凋亡和caspase-1依赖性焦亡也参与糖尿病条件下的小管细胞死亡。最近，铁下垂，一种非典型形式的铁依赖性细胞死亡，被报道导致肾脏疾病，包括急性肾损伤。通过胱氨酸/谷氨酸反转运系统Xc−(xCT)和谷胱甘肽过氧化物酶4 （GPX4）依赖机制，脂质过氧化积累引发铁死亡。本研究的目的是评估铁下垂在糖尿病诱导的肾小管损伤中的作用。采用TGF-β1刺激的近端小管上皮细胞和糖尿病小鼠模型分别进行体外和体内实验。定量测定xCT和GPX4表达、细胞活力、谷胱甘肽浓度和脂质过氧化水平，以确定铁下垂。对铁下垂抑制的效果也进行了评估。在糖尿病患者的肾活检样本中，与非糖尿病患者相比，xCT和GPX4 mRNA表达降低。在TGF-β1刺激的小管细胞中，细胞内谷胱甘肽浓度降低，脂质过氧化增强，这两者都与铁中毒相关的细胞死亡有关。铁沉陷抑制剂铁抑素-1 （ferl -1）可减轻TGF-β1诱导的铁沉陷。与对照组相比，糖尿病小鼠肾脏中xCT和GPX4 mRNA和蛋白的表达降低。小鼠肾谷胱甘肽浓度降低，脂质过氧化升高，经fe -1处理可减轻上述变化。糖尿病患者肾小管细胞死亡与铁下垂有关。抑制铁下垂可能是糖尿病肾病的一种治疗选择。
Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system Xc− (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.
登录
查看更多内容
影响因子：
3
作者：
GINEVRI, F;PICCOTTI, E;GUSMANO, R
通讯作者：
GUSMANO, R
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.3174/ajnr.a5143
发表时间：
2017-06
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Chiang GC;Mao X;Kang G;Chang E;Pandya S;Vallabhajosula S;Isaacson R;Ravdin LD;Alzheimer's Disease Neuroimaging Initiative;Shungu DC
通讯作者：
Shungu DC
影响因子：
2.5
作者：
deTorres, C;Munell, F;Macaya, A
通讯作者：
Macaya, A
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M