Long non-coding RNA HCG18 promotes M1 macrophage polarization through regulating the miR-146a/TRAF6 axis, facilitating the progression of diabetic peripheral neuropathy.
Diabetic peripheral neuropathy
Macrophage polarization
TRAF6
lncRNA HCG18
miR-146a
Journal
Molecular and cellular biochemistry
ISSN: 1573-4919
Titre abrégé: Mol Cell Biochem
Pays: Netherlands
ID NLM: 0364456
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
03
06
2020
accepted:
19
09
2020
pubmed:
1
10
2020
medline:
13
7
2021
entrez:
30
9
2020
Statut:
ppublish
Résumé
Diabetic peripheral neuropathy (DPN) is one of the most important complications in diabetes mellitus (DM), which has been reported to be modulated by long non-coding RNAs (lncRNAs). The purpose of the current study is to explore the regulatory mechanism of lncRNA HCG18 on DPN in vitro. The expression of lncRNA HCG18, miR-146a, TRAF6, CD11c, and iNOS was detected by qRT-PCR. Through Enzyme-linked immunosorbent assay, the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were determined. M1 macrophage polarization was measured by flow cytometry analysis. The interactions between miR-146a and HCG18/TRAF6 were predicted by Starbase/Targetscan software and verified by the dual luciferase reporter assay. Western blot assay was performed to determine the protein expression of TRAF6. LncRNA HCG18 was highly expressed in DPN model and HG-induced macrophages. The levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were elevated in DPN model. The expression of M1 markers (CD11c and iNOS) was visibly up-regulated in DPN model and was positively correlated with HCG18 expression. LncRNA HCG18 facilitated M1 macrophage polarization. In addition, miR-146a was identified as a target of lncRNA HCG18. Overexpression of miR-146a reversed the promoting effect of HCG18 on M1 macrophage polarization. Simultaneously, TRAF6 was a target gene of miR-146a TRAF6 expression was positively modulated by HCG18 and was negatively modulated by miR-146a. Down-regulation of TRAF6 reversed the promoting effect of HCG18 on M1 macrophage polarization. LncRNA HCG18 promotes M1 macrophage polarization via regulating the miR-146a/TRAF6 axis, facilitating the progression of DPN. This study provides a possible therapeutic strategy for DPN.
Identifiants
pubmed: 32996080
doi: 10.1007/s11010-020-03923-3
pii: 10.1007/s11010-020-03923-3
doi:
Substances chimiques
MIRN146 microRNA, rat
0
MicroRNAs
0
Mirn146 microRNA, mouse
0
RNA, Long Noncoding
0
TNF Receptor-Associated Factor 6
0
TRAF6 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
471-482Subventions
Organisme : The Science Foundation of Health Commission of Shanxi Province
ID : 20161004
Organisme : The Science Foundation of Health Commission of Shanxi Province
ID : 201601052
Organisme : The Science Foundation of Health Commission of Shanxi Province
ID : 2018GW26
Organisme : Scientific Research Foundation for outstanding youth of Shanxi Bethune Hospital
ID : 2019YJ09
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