Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts.
Animals
Cell Proliferation
/ drug effects
Cells, Cultured
Collagen
/ genetics
Disease Models, Animal
Fibrosis
Gene Silencing
Male
Methyltransferases
/ genetics
Mice
Mice, Inbred C57BL
Myocardial Infarction
/ genetics
Myocardium
/ pathology
Myofibroblasts
/ drug effects
Signal Transduction
/ drug effects
Transcriptome
Transfection
Transforming Growth Factor beta1
/ pharmacology
Up-Regulation
/ genetics
METTL3
TGF-β1
cardiac fibrosis
m6A RNA modification
myocardial infarction
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
18
12
2019
revised:
06
10
2020
accepted:
20
10
2020
pubmed:
6
11
2020
medline:
29
6
2021
entrez:
5
11
2020
Statut:
ppublish
Résumé
Cardiac fibrosis is characterized by the activation of cardiac fibroblasts and accumulation of extracellular matrix. METTL3, a component of methyltransferase complex, participates in multiple biological processes associated with mammalian development and disease progression. However, the role of METTL3 in cardiac fibrosis is still unknown. We performed fibroblasts activation with TGF-β1 (20 ng/mL) in vitro and established in vivo mouse models with lentivirus to assess the effects of METTL3 on cardiac fibroblasts proliferation and collagen formation. Methylated RNA immunoprecipitation (MeRIP) was used to define the potential fibrosis-regulated gene. The expression level of METTL3 was increased in cardiac fibrotic tissue of mice with chronic myocardial infarction and cultured cardiac fibroblats (CFs) treated with TGF-β1. Enforced expression of METTL3 promoted proliferation and fibroblast-to-myofibroblast transition and collagens accumulation, while silence of METTL3 did the opposite. Silence of METTL3 by lentivirus carrying METTL3 siRNA markedly alleviated cardiac fibrosis in MI mice. Transcriptome and N6-methyladenosine (m
Identifiants
pubmed: 33150686
doi: 10.1096/fj.201903169R
doi:
Substances chimiques
Transforming Growth Factor beta1
0
Collagen
9007-34-5
Methyltransferases
EC 2.1.1.-
Mettl3 protein, mouse
EC 2.1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21162Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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