Huagan tongluo Fang improves liver fibrosis via down-regulating miR-184 and up-regulating FOXO1 to inhibit Th17 cell differentiation.
Animals
Base Sequence
Carbon Tetrachloride
Cell Differentiation
Disease Models, Animal
Down-Regulation
/ genetics
Drugs, Chinese Herbal
/ pharmacology
Forkhead Box Protein O1
/ genetics
Liver Cirrhosis
/ drug therapy
Male
Mice, Inbred C57BL
MicroRNAs
/ genetics
Th17 Cells
/ cytology
Up-Regulation
/ genetics
FOXO1
HGTLF
Liver fibrosis
Th17 cell
miR-184
Journal
Experimental and molecular pathology
ISSN: 1096-0945
Titre abrégé: Exp Mol Pathol
Pays: Netherlands
ID NLM: 0370711
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
05
08
2019
revised:
19
03
2020
accepted:
02
05
2020
pubmed:
8
5
2020
medline:
30
10
2020
entrez:
8
5
2020
Statut:
ppublish
Résumé
The purpose of this research is to reveal the improvement effect and potential mechanism of Huagan tongluo Fang (HGTLF) on liver fibrosis. A mouse model of liver fibrosis induced by CCl HGTLF could significantly improve liver fibrosis in mice. By qRT-PCR, miR-184 was most significantly expressed after HGTLF drug stimulation, and miR-184 was considered to be the major RNA involved in Th17 cell differentiation. Interference with miR-184 in Th17 cells inhibited the differentiation of Th17 cells. By online software and dual-luciferase reporter system assay, the direct interaction of miR-184 with FOXO1 was confirmed. After HGTLF treatment of Th17 cells overexpressing miR-184, FOXO1 protein levels were significantly up-regulated and inhibited the differentiation of Th17 cells, which was reversed by miR-184 inhibitors. The Vivo experiments also confirmed the improvement effect of HGTLF on liver fibrosis in mice. Our results indicated that HGTLF could improve liver fibrosis via down-regulating miR-184 and up-regulating of FOXO1 to inhibit Th17 cell differentiation.
Sections du résumé
BACKGROUND
The purpose of this research is to reveal the improvement effect and potential mechanism of Huagan tongluo Fang (HGTLF) on liver fibrosis.
METHODS
A mouse model of liver fibrosis induced by CCl
RESULTS
HGTLF could significantly improve liver fibrosis in mice. By qRT-PCR, miR-184 was most significantly expressed after HGTLF drug stimulation, and miR-184 was considered to be the major RNA involved in Th17 cell differentiation. Interference with miR-184 in Th17 cells inhibited the differentiation of Th17 cells. By online software and dual-luciferase reporter system assay, the direct interaction of miR-184 with FOXO1 was confirmed. After HGTLF treatment of Th17 cells overexpressing miR-184, FOXO1 protein levels were significantly up-regulated and inhibited the differentiation of Th17 cells, which was reversed by miR-184 inhibitors. The Vivo experiments also confirmed the improvement effect of HGTLF on liver fibrosis in mice.
CONCLUSION
Our results indicated that HGTLF could improve liver fibrosis via down-regulating miR-184 and up-regulating of FOXO1 to inhibit Th17 cell differentiation.
Identifiants
pubmed: 32380055
pii: S0014-4800(19)30600-8
doi: 10.1016/j.yexmp.2020.104447
pii:
doi:
Substances chimiques
Drugs, Chinese Herbal
0
FOXO1 protein, human
0
Forkhead Box Protein O1
0
MIRN184 microRNA, human
0
MicroRNAs
0
tongluo
0
Carbon Tetrachloride
CL2T97X0V0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104447Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no actual or potential conflicts of interest to declare.