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Curcumin reduces LPS-induced septic acute kidney injury through suppression of lncRNA PVT1 in mice.
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-20 , DOI: 10.1016/j.lfs.2020.117340
Wei Huang 1 , Xueting Li 1 , Dawei Wang 1 , Yinghao Sun 1 , Qian Wang 1 , Yue Bu 1 , Fangfang Niu 1
Affiliation  

OBJECTIVE To investigate the protective effects of curcumin on LPS-induced septic acute kidney injury and to explore its underlying molecular mechanisms. METHODS A mouse model of septic acute kidney injury (AKI) was given an intraperitoneal injection of lipopolysaccharide (LPS), followed by administration of variable levels of curcumin (intragastric). And NRK cells were used as the kidney cell model for all in vitro studies. RESULTS Curcumin significantly decreased the levels of serum Scr, BUN, and Cyc c and reduced kidney injury in LPS-induced AKI mice. Kidney tissues of LPS-induced AKI mice showed an increase in PVT1, ED-1, TNF-α, IL-1β, IL-6, p-IkBα/IkBα, p-p65/p65, p-JNK/JNK, and p-c-JUN/c-JUN expression levels; however, treatment with curcumin significantly reduced this effect. Curcumin increased the survival rate NRK cells exposed to LPS-induced inflammation in vitro. Moreover, NRK cells that overexpressed PVT1 had lower survival rates than WT NRK cells obtained from mice that received curcumin treatment after treating with LPS. Additionally, curcumin reduced the LPS-induced increase in Bax, cleaved-caspase3/caspase 3, p-IkBα/IkBα, p-p65/p65, p-JNK/JNK, and p-c-JUN/c-JUN protein expression, and increased Bcl2 protein expression in NRK cells. However, the extent of these changes was low in NRK cells that overexpressed PVT1. CONCLUSION Curcumin decreased PVT1 expression in LPS-induced septic acute kidney tissues and reduced LPS-induced septic acute kidney injury in mice. This might be related to the inhibition of the JNK/NF-κB pathway by curcumin through suppression of lncRNA PVT1.

中文翻译:

姜黄素通过抑制小鼠lncRNA PVT1减少LPS诱导的败血性急性肾脏损伤。

目的研究姜黄素对脂多糖(LPS)诱导的败血性急性肾脏损伤的保护作用,并探讨其潜在的分子机制。方法对小鼠败血症性急性肾损伤(AKI)模型进行腹腔注射脂多糖(LPS),然后施用不同水平的姜黄素(胃内)。NRK细胞被用作所有体外研究的肾细胞模型。结果姜黄素可显着降低LPS诱导的AKI小鼠的血清Scr,BUN和Cyc c水平,并减少肾脏损伤。LPS诱导的AKI小鼠的肾脏组织显示PVT1,ED-1,TNF-α,IL-1β,IL-6,p-IkBα/IkBα,p-p65 / p65,p-JNK / JNK和pc升高-JUN / c-JUN表达水平;但是,用姜黄素治疗会明显降低这种效果。姜黄素提高了暴露于LPS诱导的炎症反应的NRK细胞的存活率。此外,过表达PVT1的NRK细胞的存活率要比从接受LPS治疗后接受姜黄素治疗的小鼠获得的WT NRK细胞低。此外,姜黄素减少了LPS诱导的Bax,裂解的caspase3 / caspase 3,p-IkBα/IkBα,p-p65 / p65,p-JNK / JNK和pc-JUN / c-JUN蛋白表达增加,并增加Bcl2蛋白在NRK细胞中的表达。但是,这些变化的程度在过表达PVT1的NRK细胞中较低。结论姜黄素可降低LPS诱发的脓毒性急性肾脏组织中PVT1的表达,并降低LPS诱发的脓毒性急性肾脏损伤。这可能与姜黄素通过抑制lncRNA PVT1抑制JNK /NF-κB途径有关。过度表达PVT1的NRK细胞的存活率低于从接受LPS治疗后接受姜黄素治疗的小鼠获得的WT NRK细胞。此外,姜黄素减少了LPS诱导的Bax,裂解的caspase3 / caspase 3,p-IkBα/IkBα,p-p65 / p65,p-JNK / JNK和pc-JUN / c-JUN蛋白表达增加,并增加Bcl2蛋白在NRK细胞中的表达。但是,这些变化的程度在过表达PVT1的NRK细胞中较低。结论姜黄素可降低LPS诱导的脓毒性急性肾脏组织中PVT1的表达,并降低LPS诱导的脓毒性急性肾脏损伤。这可能与姜黄素通过抑制lncRNA PVT1抑制JNK /NF-κB途径有关。过度表达PVT1的NRK细胞的存活率低于从接受LPS治疗后接受姜黄素治疗的小鼠获得的WT NRK细胞。此外,姜黄素减少了LPS诱导的Bax,裂解的caspase3 / caspase 3,p-IkBα/IkBα,p-p65 / p65,p-JNK / JNK和pc-JUN / c-JUN蛋白表达增加,并增加Bcl2蛋白在NRK细胞中的表达。但是,这些变化的程度在过表达PVT1的NRK细胞中较低。结论姜黄素可降低LPS诱导的脓毒性急性肾脏组织中PVT1的表达,并降低LPS诱导的脓毒性急性肾脏损伤。这可能与姜黄素通过抑制lncRNA PVT1抑制JNK /NF-κB途径有关。
更新日期:2020-01-20
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