Tim-3 protects against cisplatin nephrotoxicity by inhibiting NF-κB-mediated inflammation.
Tim-3 protects against cisplatin nephrotoxicity by inhibiting NF-κB-mediated inflammation.
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Tim-3 通过抑制 NF-κB 介导的炎症来防止顺铂肾毒性。
DOI：
10.1038/s41420-023-01519-6
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发表时间：
2023-07-01
影响因子：
7
通讯作者：
Lou, Qiang
中科院分区：
文献类型：
--
作者：
Li, Peiyao;Li, Xuemiao;Wu, Wenbin;Hou, Mengjia;Yin, Guanyi;Wang, Zhonghang;Du, Ziyu;Ma, Yuanfang;Wei, Yinxiang;Lou, Qiang
本研究探讨了Tim-3（T细胞免疫球蛋白和粘蛋白结构域蛋白3）对顺铂诱导的急性肾损伤的影响。顺铂以时间依赖性方式诱导小鼠肾组织和近端小管来源的BUMPT细胞中的Tim-3表达。与野生型小鼠相比，Tim-3基因敲除小鼠的血清肌酸酐和尿素氮水平更高，TUNEL染色信号增强，8-OHdG（8-羟基-2 ' -脱氧鸟苷）积聚更严重，caspase 3的切割增加。纯化的可溶性Tim-3（sTim-3）蛋白通过竞争性结合Tim-3配体来干预顺铂刺激的BUMPT细胞。sTim-3明显增加顺铂诱导的细胞凋亡。在顺铂治疗条件下，Tim-3敲除或sTim-3促进TNF-α（肿瘤坏死因子-α）和IL-1β（白细胞介素-1 β）的表达，并抑制IL-10（白细胞介素-10）的表达。NF-κB（nuclear factor kappa light chain enhancer of activated B cells）P65抑制剂PDTC或TPCA 1可降低顺铂处理的Tim-3基因敲除小鼠血清中升高的肌酐和BUN（blood urea nitrogen）水平，并降低sTim-3和顺铂处理的BUMPT细胞中caspase 3裂解的增加。此外，sTim-3增强顺铂诱导的BUMPT细胞中的线粒体氧化应激，这可以通过PDTC来减轻。这些数据表明Tim-3可能通过抑制NF-κ B介导的炎症和氧化应激来保护肾损伤。
The impact of Tim-3 (T cell immunoglobulin and mucin domain-containing protein 3) on cisplatin-induced acute kidney injury was investigated in this study. Cisplatin-induced Tim-3 expression in mice kidney tissues and proximal tubule-derived BUMPT cells in a time-dependent manner. Compared with wild-type mice, Tim-3 knockout mice have higher levels of serum creatinine and urea nitrogen, enhanced TUNEL staining signals, more severe 8-OHdG (8-hydroxy-2’ -deoxyguanosine) accumulation, and increased cleavage of caspase 3. The purified soluble Tim-3 (sTim-3) protein was used to intervene in cisplatin-stimulated BUMPT cells by competitively binding to the Tim-3 ligand. sTim-3 obviously increased the cisplatin-induced cell apoptosis. Under cisplatin treatment conditions, Tim-3 knockout or sTim-3 promoted the expression of TNF-α (tumor necrosis factor-alpha) and IL-1β (Interleukin-1 beta) and inhibited the expression of IL-10 (interleukin-10). NF-κB (nuclear factor kappa light chain enhancer of activated B cells) P65 inhibitor PDTC or TPCA1 lowed the increased levels of creatinine and BUN (blood urea nitrogen) in cisplatin-treated Tim-3 knockout mice serum and the increased cleavage of caspase 3 in sTim-3 and cisplatin-treated BUMPT cells. Moreover, sTim-3 enhanced mitochondrial oxidative stress in cisplatin-induced BUMPT cells, which can be mitigated by PDTC. These data indicate that Tim-3 may protect against renal injury by inhibiting NF-κB-mediated inflammation and oxidative stress.
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影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
影响因子：
9.7
作者：
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通讯作者：
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影响因子：
6
作者：
Schroll, Andrea;Eller, Kathrin;Rosenkranz, Alexander R.
通讯作者：
Rosenkranz, Alexander R.
影响因子：
11.4
作者：
Haubner S;Perna F;Köhnke T;Schmidt C;Berman S;Augsberger C;Schnorfeil FM;Krupka C;Lichtenegger FS;Liu X;Kerbs P;Schneider S;Metzeler KH;Spiekermann K;Hiddemann W;Greif PA;Herold T;Sadelain M;Subklewe M
通讯作者：
Subklewe M
T 细胞 TIM3 表达在慢性肾脏炎症中的新作用
影响因子：
7.3
作者：
Lu C;Chen H;Wang C;Yang F;Li J;Liu H;Chen G
通讯作者：
Chen G