Abstract:
BACKGROUND:Ischemia-reperfusion (IR) causes acute kidney injury (AKI), and ischemia pretreatment may exert protection. Mitogen-activated protein kinase kinase 3 (MKK3), which is involved in the signal transduction pathway in IR-induced injury, is a potential target of miR-21. We aimed to verify the targeting regulation of miR-21 on MKK3 and to explore the effects of miR-21-mediated MKK3 expression changes in AKI. METHODS:Vectors containing the MKK3 3'UTR and mutated MKK3-3U-M were constructed and co-transfected with nonsense miR, miR-21-5p mimics or inhibitor in HEK293 cells. Gene expressions were detected by dual luciferase reporter assay. The effects of miR-21 on mRNA and protein of MKK3 were investigated in HK-2 cells. Male C57BL/6J mice were treated with ischemic preconditioning (IPC) and IR. Kidney functions were assessed through monitoring serum creatinine (Scr) and blood urea nitrogen (BUN). Pathological changes were observed and scored with histological samples of kidney. Expression levels of miR-21, MKK3, interleukin (IL)-6, tumor necrosis factor (TNF)-α before and after IPC and IR were examined by real-time polymerase chain reaction and/or immunohistochemistry. RESULTS:miR-21 regulated the expression of MKK3 via 3'UTR. Following IR, MKK3, IL-6 and TNF-α levels were increased. Scr, BUN and pathological injuries were aggravated, and miR-21 expression was increased. IPC increased miR-21 levels ahead of IR and inhibited the increases in MKK3, IL-6 and TNF-α levels and the aggravation of Scr, BUN and pathological injuries. CONCLUSIONS:miR-21 targets MKK3 in vivo and in vitro, inhibiting the downstream factors IL-6 and TNF-α. Therefore, miR-21 might be involved in protection of IPC against IR of the kidney.
journal_name
J Nephroljournal_title
Journal of nephrologyauthors
Li Z,Deng X,Kang Z,Wang Y,Xia T,Ding N,Yin Ydoi
10.1007/s40620-015-0217-xsubject
Has Abstractpub_date
2016-02-01 00:00:00pages
27-36issue
1eissn
1121-8428issn
1724-6059pii
10.1007/s40620-015-0217-xjournal_volume
29pub_type
杂志文章abstract::Thales was born into a noble family of Phoenician origin at the time of the 25th Olympiad (floruit 585 bc; he was 40 in the year of the solar eclipse. He had no teachers but had occasion to learn from Egyptian priests. He developed into a scholar and politician very much appreciated by Heraclitus, Herodotus and Democr...
journal_title:Journal of nephrology
pub_type: 传,历史文章,杂志文章
doi:
更新日期:2009-11-01 00:00:00
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journal_title:Journal of nephrology
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pub_type: 杂志文章
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journal_title:Journal of nephrology
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journal_title:Journal of nephrology
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pub_type: 杂志文章
doi:
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journal_title:Journal of nephrology
pub_type: 杂志文章
doi:10.1007/s40620-016-0352-z
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journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1998-11-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
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pub_type: 历史文章,杂志文章
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更新日期:2011-05-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2004-11-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 00:00:00
abstract:BACKGROUND:In older patients with chronic kidney disease (CKD), the risk of progression to end stage renal disease and cardiovascular death both differ compared to younger patients. This likely reflects differences in case mix and co-morbid burdens. We sought to establish the extent to which age itself is an independen...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:10.1007/s40620-018-0529-8
更新日期:2018-12-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
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pub_type: 杂志文章,随机对照试验
doi:10.1007/s40620-014-0039-2
更新日期:2014-04-01 00:00:00
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pub_type: 杂志文章,实务指引
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journal_title:Journal of nephrology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:2001-11-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章,评审
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pub_type: 历史文章,杂志文章
doi:
更新日期:2004-03-01 00:00:00
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journal_title:Journal of nephrology
pub_type: 杂志文章
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journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.5301/jn.5000233
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Journal of nephrology
pub_type: 杂志文章
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