Berberine Acts on C/EBPβ/lncRNA Gas5/miR-18a-5p Loop to Decrease the Mitochondrial ROS Generation in HK-2 Cells.
Animals
Apoptosis
Berberine
/ pharmacology
CCAAT-Enhancer-Binding Protein-beta
/ genetics
Diabetes Mellitus, Experimental
/ complications
Diabetes Mellitus, Type 2
/ complications
Diabetic Nephropathies
/ drug therapy
Gene Expression Regulation
/ drug effects
Humans
Kidney Tubules, Proximal
/ drug effects
MicroRNAs
/ genetics
Prognosis
RNA, Long Noncoding
/ genetics
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
/ metabolism
Signal Transduction
C/EBPβ
Gas5
berberine
diabetic nephropathy
reactive oxygen species
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
03
2021
accepted:
02
08
2021
entrez:
16
9
2021
pubmed:
17
9
2021
medline:
21
12
2021
Statut:
epublish
Résumé
Berberine (BBR) has therapeutic effect on diabetic nephropathy (DN), but its molecular mechanism is not completely clear. The DN model was established to observe the therapeutic effect of BBR. The expression levels of lncRNA Gas5 were detected by PCR. The transcriptional regulation of CCAAT enhancer binding protein beta (C/EBPβ) on Gas5 was analyzed by chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and luciferase reporter gene assay. The targeted regulation between Gas5 and miR-18a-5p and between miR-18a-5p and C/EBPβ 3'-untranslated region (3'-UTR) was also analyzed. In HG environment, BBR decreased the mitochondrial reactive oxygen species (ROS) generation and activated the C/EBPβ expression in HK-2 cells; C/EBPβ could combine with the reaction element on the promoter of Gas5 to promote its expression. Gas5 also inhibited the miR-18a-5p expression as competing endogenous RNA (ceRNA) and reduce the negative regulatory effect of miR-18a-5p on C/EBPβ. BBR could activate C/EBPβ/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signal pathway, regulate mitochondrial energy metabolism, and inhibit ROS production and apoptosis by activating C/EBPβ/Gas5/miR-18a-5p positive feedback loop in HG environment. It also showed that BBR alleviated streptozotocin (STZ) induced renal injury in DN rats This study suggested that BBR could regulate the mitochondrial ROS generation by activating the positive feedback loop of C/EBPβ/Gas5/miR-18a-5p.
Sections du résumé
Background
Berberine (BBR) has therapeutic effect on diabetic nephropathy (DN), but its molecular mechanism is not completely clear.
Methods
The DN model was established to observe the therapeutic effect of BBR. The expression levels of lncRNA Gas5 were detected by PCR. The transcriptional regulation of CCAAT enhancer binding protein beta (C/EBPβ) on Gas5 was analyzed by chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and luciferase reporter gene assay. The targeted regulation between Gas5 and miR-18a-5p and between miR-18a-5p and C/EBPβ 3'-untranslated region (3'-UTR) was also analyzed.
Results
In HG environment, BBR decreased the mitochondrial reactive oxygen species (ROS) generation and activated the C/EBPβ expression in HK-2 cells; C/EBPβ could combine with the reaction element on the promoter of Gas5 to promote its expression. Gas5 also inhibited the miR-18a-5p expression as competing endogenous RNA (ceRNA) and reduce the negative regulatory effect of miR-18a-5p on C/EBPβ. BBR could activate C/EBPβ/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signal pathway, regulate mitochondrial energy metabolism, and inhibit ROS production and apoptosis by activating C/EBPβ/Gas5/miR-18a-5p positive feedback loop in HG environment. It also showed that BBR alleviated streptozotocin (STZ) induced renal injury in DN rats
Conclusions
This study suggested that BBR could regulate the mitochondrial ROS generation by activating the positive feedback loop of C/EBPβ/Gas5/miR-18a-5p.
Identifiants
pubmed: 34526965
doi: 10.3389/fendo.2021.675834
pmc: PMC8435884
doi:
Substances chimiques
CCAAT-Enhancer-Binding Protein-beta
0
CEBPB protein, human
0
GAS5 long non-coding RNA, human
0
MIRN18A microRNA, human
0
MicroRNAs
0
RNA, Long Noncoding
0
Reactive Oxygen Species
0
Berberine
0I8Y3P32UF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
675834Informations de copyright
Copyright © 2021 Xu, Liu, Gan, Hu, Xiang, Xing, Zhu and Ye.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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