PMID- 32581828
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 11
DP  - 2020
TI  - MiR-181d-5p Targets KLF6 to Improve Ischemia/Reperfusion-Induced AKI Through 
      Effects on Renal Function, Apoptosis, and Inflammation.
PG  - 510
LID - 10.3389/fphys.2020.00510 [doi]
LID - 510
AB  - Renal tubular epithelial cell (RTEC) death and renal interstitial inflammation 
      are the most crucial pathophysiological changes in acute kidney 
      ischemia/reperfusion injury (IRI). The microRNA (miR)-181d family plays diverse 
      roles in cell proliferation, apoptosis and inflammation, but its renal target and 
      potential role in IRI are unknown. Here, we showed that the expression of 
      miR-181d-5p decreased and Krueppel-like factor 6 (KLF6) increased in a renal cell 
      (HK-2) model of hypoxia/reoxygenation (H/R) injury and a mouse model of renal 
      IRI. They were mainly distributed in the renal tubules. After renal IRI, 
      miR-181d-5p overexpression significantly inhibited inflammatory mediators, 
      reduced apoptosis and further improved renal function. KLF6 exacerbated RTEC 
      damage and acted as a NF-kappaB co-activator to aggravate the renal IRI inflammatory 
      response. Mechanistically, KLF6 was predicted as a new potential target gene of 
      miR-181d-5p through bioinformatic analysis and luciferase reporter assay 
      verification. After overexpressing miR-181d-5p and inhibiting KLF6, the role of 
      miR-181d-5p was weakened on the renal damage improvement. In conclusion, 
      miR-181d-5p upregulation produced protective antiapoptotic and anti-inflammatory 
      effects against IRI in kidneys in vivo and H/R injury in HK-2 cells in vitro, and 
      these effects were achieved by targeted inhibition of KLF6. Thus, our results 
      provide novel insights into the molecular mechanisms associated with IRI and a 
      potential novel therapeutic target.
CI  - Copyright (c) 2020 Zhang, Li, Guan, Zhou, Wang, Yang, Zhen, Dai, Zhao, Jiang and 
      Xu.
FAU - Zhang, Yue
AU  - Zhang Y
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Li, Chenyu
AU  - Li C
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
AD  - Nephrologisches Zentrum, Ludwig Maximilian University of Munich, Munich, Germany.
FAU - Guan, Chen
AU  - Guan C
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Zhou, Bin
AU  - Zhou B
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Wang, Lin
AU  - Wang L
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Yang, Chengyu
AU  - Yang C
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Zhen, Li
AU  - Zhen L
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Dai, Jie
AU  - Dai J
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Zhao, Long
AU  - Zhao L
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Jiang, Wei
AU  - Jiang W
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Xu, Yan
AU  - Xu Y
AD  - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20200527
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC7295155
OTO - NOTNLM
OT  - IRI
OT  - KLF6
OT  - MiR-181d-5p
OT  - apoptosis
OT  - inflammation
OT  - renal function
EDAT- 2020/06/26 06:00
MHDA- 2020/06/26 06:01
PMCR- 2020/05/27
CRDT- 2020/06/26 06:00
PHST- 2020/02/27 00:00 [received]
PHST- 2020/04/27 00:00 [accepted]
PHST- 2020/06/26 06:00 [entrez]
PHST- 2020/06/26 06:00 [pubmed]
PHST- 2020/06/26 06:01 [medline]
PHST- 2020/05/27 00:00 [pmc-release]
AID - 10.3389/fphys.2020.00510 [doi]
PST - epublish
SO  - Front Physiol. 2020 May 27;11:510. doi: 10.3389/fphys.2020.00510. eCollection 
      2020.