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Content Provider | PubMed Central |
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Author | Dai, Yan Jia, Ping Fang, Yi Liu, Hong Jiao, Xiaoyan He, John C. Ding, Xiaoqiang |
Copyright Year | 2016 |
Abstract | MicroRNA-146a is one of most important microRNAs involved in development of endotoxin tolerance via (toll-like receptors) TLRs/ NF-κB pathway. In this study, we sought to identify the mechanistic role of miR-146a in mediating the protective effect of lipopolysaccharide (LPS) pretreatment on kidney ischemia/reperfusion injury. A locked nucleic acid–modified anti-miR-146a given before LPS treatment knocked down miR-146a expression and completely negated LPS-mediated protection against kidney ischemia/reperfusion injury. Knockdown of miR-146a resulted in significantly higher histopathological scores for tubular damage, expression of proinflammatory cytokines and chemokines, and neutrophil and macrophage infiltration. Furthermore, knockdown of miR-146a greatly up-regulated the protein levels of IL-1 receptor-associated kinase (IRAK-1) and tumor-necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which are known target genes of miR-146a, leading to activation of NF-κB. Finally, elevation of nuclear translocation of NF-κB p65/p50 and caspase-3 expression, degradation of cytosolic IkBα and BcL-xL, and substantially exacerbation of tubular cell apoptosis were inversely correlated with miR-146a expression. Taken together, our results identify that miR146a exerts a kidney protective effect through negative regulation of acute inflammatory response by suppressing NF-κB activation and proinflammatory genes expression. |
Related Links | http://dx.doi.org/10.1038/srep27091 |
Starting Page | 27091 |
File Format | |
ISSN | 20452322 |
e-ISSN | 20452322 |
Journal | Scientific Reports |
Volume Number | 6 |
Language | English |
Publisher | Nature Publishing Group |
Publisher Date | 2016-06-01 |
Access Restriction | Open |
Rights Holder | Nature Publishing Group |
Subject Keyword | Science and technology Research in Higher Education |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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