miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation.
miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation.
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miR-21 通过防止上皮细胞凋亡和抑制树突状细胞成熟来预防缺血/再灌注引起的急性肾损伤
DOI：
10.3389/fphys.2018.00790
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发表时间：
2018
影响因子：
4
通讯作者：
Ding X
中科院分区：
文献类型：
--
作者：
Song N;Zhang T;Xu X;Lu Z;Yu X;Fang Y;Hu J;Jia P;Teng J;Ding X
缺氧引起的肾小管损伤和先天免疫反应是急性肾损伤的重要因素。越来越多的证据表明，miR-21过表达可以防止肾缺血损伤。此外，miR-21作为树突状细胞成熟的关键抑制剂出现。因此，我们假设miR-21通过抑制上皮细胞损伤和炎症反应来保护肾脏免受IR损伤。在本研究中，我们在体外和体内研究了miR-21及其信号通路（PTEN/AKT/mTOR/HIF, PDCD4/NFκ-B）对肾脏缺血再灌注（IR）损伤的影响。结果显示，IR在体内和体外均可增加miR-21、HIF1α和2α的表达。MiR-21通过PTEN/AKT/mTOR途径与HIF1α和2α相互作用。此外，miR-21的抑制激活了PDCD4/NFκ-B通路，这对树突状细胞成熟至关重要。肾IR通过诱导树突状细胞成熟和促进IL-12、IL-6和TNF-α细胞因子的分泌来触发局部炎症。miR-21的敲低增强了IR对小管上皮细胞凋亡和树突状细胞成熟的影响。我们的研究结果表明，IR诱导的miR-21通过与HIF （PTEN/AKT/mTOR/HIF/miR-21）的反馈相互作用以及通过PDCD4/NF-κB途径抑制dc的成熟来保护上皮细胞免受IR损伤。这些发现强调了AKI新的治疗机会。
Renal tubular injury and innate immune responses induced by hypoxia contribute to acute kidney injury. Accumulating evidence suggests that miR-21 overexpression protects against kidney ischemia injury. Additionally, miR-21 emerges as a key inhibitor in dendritic cell maturation. Thus, we hypothesized that miR-21 protects the kidney from IR injury by suppressing epithelial cell damage and inflammatory reaction. In this study, we investigated effects of miR-21 and its signaling pathways (PTEN/AKT/mTOR/HIF, PDCD4/NFκ-B) on kidney ischemia/reperfusion (IR) injury in vitro and in vivo. The results revealed that IR increased miR-21, HIF1α, and 2α expression in vivo and in vitro. MiR-21 interacted with HIF1α and 2α through the PTEN/AKT/mTOR pathway. Moreover, inhibition of miR-21 activated PDCD4/NFκ-B pathways, which are critical for dendritic cell maturation. Renal IR triggers local inflammation by inducing the dendritic cell maturation and promoting the secretion of IL-12, IL-6, and TNF-α cytokines. Knockdown of miR-21 intensified the effect of IR on tubular epithelial cell apoptosis and dendritic cell maturation. Our results suggested that IR-inducible miR-21 protects epithelial cells from IR injury via a feedback interaction with HIF (PTEN/AKT/mTOR/HIF/miR-21) and by inhibiting maturation of DCs through the PDCD4/NF-κB pathway. These findings highlight new therapeutic opportunities in AKI.
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影响因子：
3.7
作者：
Conde E;Alegre L;Blanco-Sánchez I;Sáenz-Morales D;Aguado-Fraile E;Ponte B;Ramos E;Sáiz A;Jiménez C;Ordoñez A;López-Cabrera M;del Peso L;de Landázuri MO;Liaño F;Selgas R;Sanchez-Tomero JA;García-Bermejo ML
通讯作者：
García-Bermejo ML
影响因子：
19.6
作者：
Dong, X.;Swaminathan, S.;Griffin, M. D.
通讯作者：
Griffin, M. D.
影响因子：
21.1
作者：
Li, Yongkui;Xie, Jiajia;Zhu, Ying
通讯作者：
Zhu, Ying
影响因子：
--
作者：
Lin, Qinqin;Geng, Yuanwen;Tian, Zhenjun
通讯作者：
Tian, Zhenjun
影响因子：
6.1
作者：
Gaede, Luise;Liebetrau, Christoph;Moellmann, Helge
通讯作者：
Moellmann, Helge