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miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation

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 hypothesize...

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Autores principales: Song, Nana, Zhang, Ting, Xu, XiaLian, Lu, Zhihui, Yu, Xiaofang, Fang, Yi, Hu, Jiachang, Jia, Ping, Teng, Jie, Ding, Xiaoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036242/
https://www.ncbi.nlm.nih.gov/pubmed/30013485
http://dx.doi.org/10.3389/fphys.2018.00790
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author Song, Nana
Zhang, Ting
Xu, XiaLian
Lu, Zhihui
Yu, Xiaofang
Fang, Yi
Hu, Jiachang
Jia, Ping
Teng, Jie
Ding, Xiaoqiang
author_facet Song, Nana
Zhang, Ting
Xu, XiaLian
Lu, Zhihui
Yu, Xiaofang
Fang, Yi
Hu, Jiachang
Jia, Ping
Teng, Jie
Ding, Xiaoqiang
author_sort Song, Nana
collection PubMed
description 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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spelling pubmed-60362422018-07-16 miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation Song, Nana Zhang, Ting Xu, XiaLian Lu, Zhihui Yu, Xiaofang Fang, Yi Hu, Jiachang Jia, Ping Teng, Jie Ding, Xiaoqiang Front Physiol Physiology 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. Frontiers Media S.A. 2018-06-26 /pmc/articles/PMC6036242/ /pubmed/30013485 http://dx.doi.org/10.3389/fphys.2018.00790 Text en Copyright © 2018 Song, Zhang, Xu, Lu, Yu, Fang, Hu, Jia, Teng and Ding. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Song, Nana
Zhang, Ting
Xu, XiaLian
Lu, Zhihui
Yu, Xiaofang
Fang, Yi
Hu, Jiachang
Jia, Ping
Teng, Jie
Ding, Xiaoqiang
miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation
title miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation
title_full miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation
title_fullStr miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation
title_full_unstemmed miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation
title_short miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation
title_sort mir-21 protects against ischemia/reperfusion-induced acute kidney injury by preventing epithelial cell apoptosis and inhibiting dendritic cell maturation
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036242/
https://www.ncbi.nlm.nih.gov/pubmed/30013485
http://dx.doi.org/10.3389/fphys.2018.00790
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