PMID- 33383483
OWN - NLM
STAT- MEDLINE
DCOM- 20210408
LR  - 20210719
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 535
DP  - 2021 Jan 8
TI  - miR-30b-5p modulate renal epithelial-mesenchymal transition in diabetic 
      nephropathy by directly targeting SNAI1.
PG  - 12-18
LID - S0006-291X(20)32025-8 [pii]
LID - 10.1016/j.bbrc.2020.10.096 [doi]
AB  - OBJECT: Renal tubulointerstitial fibrosis plays a significant role in the 
      development of diabetic nephropathy (DN). SNAI1 is a main activator of 
      epithelial-to-mesenchymal transition (EMT) in the process of fibrosis. This study 
      aimed to investigate the effect of miR-30b-5p targeting SNAI1 on the EMT in DN. 
      METHODS: Bioinformatics and miRNAs microarray analyses were used to predict the 
      candidate miRNA targeting SNAI1, that is miR-30b-5p. The db/db mice was as DN 
      animal model and renal tissues of mice were stained with PAS. The miR-30b-5p 
      expression in mouse and human renal tissue were examined by quantitative RT-PCR 
      (qRT-PCR) and fluorescence in situ hybridization (FISH), while SNAI1 expression 
      was determined by qRT-PCR and immunohistochemistry. Luciferase reporter gene 
      assay was used to confirm miR-30b-5p directly target 3'-UTR of the SNAI1 mRNA. 
      In vitro, HK-2 cells were treated with high glucose to establish hyperglycemia 
      cell model and transfected with miR-30b-5p mimics to overexpress miR-30b-5p. 
      Expression of miR-30b-5p, SNAI1 and EMT related indicators (E-cadherin, a-SMA and 
      Vimentin) in HK-2 cells under different treatments were determined by qRT-PCR 
      and/or western-blot. In addition, immunofluorescence was performed to evaluate 
      a-SMA expression in HK-2 cells under different treatments. RESULTS: 
      Bioinformatics analyses revealed miR-30b-5p had complementary sequences with 
      SNAI1 mRNA and the seed region of miR-30b-5p was conserved in human and a variety 
      of animals, including mice. Microarray analysis showed miR-30b expression 
      decreased in DN mice, which was further verified in db/db mice by qRT-PCR and in 
      human DN by FISH. Contrary to miR-30b-5p, SNAI1 expression level was upregulated 
      in db/db mice. Correlation analysis suggested SNAI1 mRNA level was negatively 
      with miR-30b-5p level in renal tissue of db/db mice. Luciferase reporter gene 
      assay confirmed miR-30b-5p directly targeted SNAI1 mRNA. In high glucose induced 
      HK-2 cells, expression levels of miR-30b-5p and E-cadherin were decreased, while 
      SNAI1, a-SMA and Vimentin were increased. Overexpression miR-30b-5p in high 
      glucose induced HK-2 cells could reverse that phenomenon to some extent. 
      CONCLUSION: These findings suggest that miR-30b-5p play a protective role by 
      targeting SNAI1 in renal EMT in DN.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Wang, Yanzhe
AU  - Wang Y
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Liu, Yuyuan
AU  - Liu Y
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Zhang, Ling
AU  - Zhang L
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Bai, Linnan
AU  - Bai L
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Chen, Sijia
AU  - Chen S
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Sun, Linlin
AU  - Sun L
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China. Electronic address: 
      llsunzj@sina.com.
FAU - Wang, Xiaoxia
AU  - Wang X
AD  - Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China. Electronic address: 
      Omaha198501@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201229
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cadherins)
RN  - 0 (MIRN30b microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn30d microRNA, mouse)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snai1 protein, mouse)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Vimentin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cadherins/metabolism
MH  - Cell Line
MH  - Diabetic Nephropathies/*genetics/*pathology
MH  - *Epithelial-Mesenchymal Transition/drug effects
MH  - Fibrosis/genetics/pathology
MH  - Glucose/pharmacology
MH  - Humans
MH  - Hyperglycemia/genetics/pathology
MH  - Kidney/*metabolism/pathology
MH  - Kidney Diseases/genetics/pathology
MH  - Male
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Snail Family Transcription Factors/*genetics
MH  - Vimentin/metabolism
OTO - NOTNLM
OT  - Diabetic kidney disease (DN)
OT  - Epithelial-to-mesenchymal transition (EMT)
OT  - SNAI1
OT  - miR-30b-5p
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/01/01 06:00
MHDA- 2021/04/10 06:00
CRDT- 2020/12/31 20:16
PHST- 2020/10/07 00:00 [received]
PHST- 2020/10/29 00:00 [accepted]
PHST- 2021/01/01 06:00 [pubmed]
PHST- 2021/04/10 06:00 [medline]
PHST- 2020/12/31 20:16 [entrez]
AID - S0006-291X(20)32025-8 [pii]
AID - 10.1016/j.bbrc.2020.10.096 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Jan 8;535:12-18. doi: 
      10.1016/j.bbrc.2020.10.096. Epub 2020 Dec 29.