PMID- 32667078
OWN - NLM
STAT- MEDLINE
DCOM- 20210322
LR  - 20210322
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 9
DP  - 2020 Sep
TI  - Depletion of miR-21 in dendritic cells aggravates renal ischemia-reperfusion 
      injury.
PG  - 11729-11740
LID - 10.1096/fj.201903222RR [doi]
AB  - Dendritic cells (DCs) play an important role in the pathophysiology of renal 
      ischemia-reperfusion injury (IRI). The mechanisms underlying DCs phenotypic 
      modulation and their function are not fully understood. In this study, we 
      examined the effect of miR-21 on the phenotypic modulation of DCs in vitro and in 
      vivo, and further investigated the impact of miR-21-overexpression DC or 
      miR-21-deficient DC on renal IRI. We found that treatment with 
      hypoxia/reoxygenation (H/R) suppressed miR-21 expression in bone marrow-derived 
      dendritic cells (BMDCs), and significantly increased the percentage of mature DCs 
      (CD11c(+) /MHC-II(+) /CD80(+) ). Using a selection of microRNA mimics, we 
      successfully induced the upregulation of miR-21 in BMDCs, which induced immature 
      DC phenotype and an anti-inflammatory DC response. However, deletion of miR-21 in 
      BMDCs promoted maturation of DCs under H/R. Adoptive transfer of 
      miR-21-overexpression BMDCs could alleviate renal IR-induced pro-inflammatory 
      cytokines production and acute kidney injury (AKI). Mice with miR-21 deficiency 
      in DCs subjected to renal IR showed more severe renal dysfunction and 
      inflammatory response compared with wild-type mice. In addition, chemokine C 
      receptor 7 (CCR7), a surface marker of mature DC, was a target gene of miR-21, 
      and silencing of CCR7 in BMDCs led to reduced mature DCs under H/R. In 
      conclusion, our findings highlight miR-21 as a key regulator of DCs subset 
      phenotype and a potential therapeutic target in renal IRI.
CI  - (c) 2020 Federation of American Societies for Experimental Biology.
FAU - Jia, Ping
AU  - Jia P
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
AD  - Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China.
FAU - Pan, Tianyi
AU  - Pan T
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
AD  - Shanghai Medical Association, Shanghai, China.
FAU - Xu, Sujuan
AU  - Xu S
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Fang, Yi
AU  - Fang Y
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Song, Nana
AU  - Song N
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Guo, Man
AU  - Guo M
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Liang, Yiran
AU  - Liang Y
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Xu, Xialian
AU  - Xu X
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Ding, Xiaoqiang
AU  - Ding X
AD  - Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
AD  - Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China.
AD  - Shanghai Medical Center of Kidney, Shanghai, China.
AD  - Kidney and Dialysis Institute of Shanghai, Shanghai, China.
AD  - Hemodialysis Quality Control Center of Shanghai, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200715
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (MIRN-21 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, CCR7)
SB  - IM
MH  - Acute Kidney Injury/genetics/metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Dendritic Cells/*metabolism
MH  - *Gene Expression Regulation
MH  - Kidney/*metabolism/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - MicroRNAs/*genetics
MH  - Receptors, CCR7/genetics/metabolism
MH  - Reperfusion Injury/*genetics/metabolism
OTO - NOTNLM
OT  - acute kidney injury
OT  - dendritic cell
OT  - inflammation
OT  - microRNAs
EDAT- 2020/07/16 06:00
MHDA- 2021/03/23 06:00
CRDT- 2020/07/16 06:00
PHST- 2019/12/23 00:00 [received]
PHST- 2020/06/17 00:00 [revised]
PHST- 2020/06/18 00:00 [accepted]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2021/03/23 06:00 [medline]
PHST- 2020/07/16 06:00 [entrez]
AID - 10.1096/fj.201903222RR [doi]
PST - ppublish
SO  - FASEB J. 2020 Sep;34(9):11729-11740. doi: 10.1096/fj.201903222RR. Epub 2020 Jul 
      15.