Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model.
Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model.
复制标题
铁死亡是治疗 5/6 肾切除诱导的 CKD 大鼠模型中肾损伤和纤维化的新靶点。
DOI：
10.1038/s41420-022-00931-8
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发表时间：
2022-03-22
影响因子：
7
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Wang J;Wang Y;Liu Y;Cai X;Huang X;Fu W;Wang L;Qiu L;Li J;Sun L
铁下垂是一种非传统形式的调节细胞死亡，其特点是铁超载和脂质过氧化。迄今为止，对慢性肾脏疾病(CKD)中铁下垂的研究非常有限。本研究建立了5/6肾切除术大鼠CKD模型，用顺铂（CDDP）和甲磺酸去铁胺（DFO）治疗CKD大鼠，观察其病理变化（损伤标志物、纤维化）和生化指标。CKD组大鼠肾铁沉积、脂质过氧化、线粒体缺陷、铁下垂标志物诱导、TUNEL染色阳性。此外，CDDP或DFO治疗通过影响铁下垂而不是细胞凋亡来影响肾损伤和纤维化，铁下垂发生在残肾中是由于铁代谢紊乱。总之，我们的研究首次表明5/6肾切除术导致残肾铁下垂，并阐明了其潜在的发病机制。此外，我们证明铁下垂参与CKD的进展，并代表慢性肾损伤和肾纤维化的治疗靶点。
Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.
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DOI：
10.1016/s0140-6736(18)31694-5
发表时间：
2018-11-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
Foreman KJ;Marquez N;Dolgert A;Fukutaki K;Fullman N;McGaughey M;Pletcher MA;Smith AE;Tang K;Yuan CW;Brown JC;Friedman J;He J;Heuton KR;Holmberg M;Patel DJ;Reidy P;Carter A;Cercy K;Chapin A;Douwes-Schultz D;Frank T;Goettsch F;Liu PY;Nandakumar V;Reitsma MB;Reuter V;Sadat N;Sorensen RJD;Srinivasan V;Updike RL;York H;Lopez AD;Lozano R;Lim SS;Mokdad AH;Vollset SE;Murray CJL
通讯作者：
Murray CJL
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
CKD 中的 AKI：损伤加剧、修复受到抑制及其潜在机制
影响因子：
19.6
作者：
He L;Wei Q;Liu J;Yi M;Liu Y;Liu H;Sun L;Peng Y;Liu F;Venkatachalam MA;Dong Z
通讯作者：
Dong Z
影响因子：
20.3
作者：
Recalcati, S;Taramelli, D;Cairo, G
通讯作者：
Cairo, G
影响因子：
6.7
作者：
Sola-Riera, Carles;Garcia, Marina;Klingstrom, Jonas
通讯作者：
Klingstrom, Jonas