miR-146a modulates TLR1/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes.
Acne Vulgaris
/ genetics
Adult
Case-Control Studies
Cell Proliferation
Cells, Cultured
GTP-Binding Protein gamma Subunits
/ genetics
Gene Expression Regulation
Humans
Inflammation
/ genetics
Lipids
/ analysis
Lipogenesis
Male
MicroRNAs
/ genetics
RNA-Seq
Sebaceous Glands
/ immunology
Toll-Like Receptor 1
/ genetics
Toll-Like Receptor 2
/ genetics
Toll-Like Receptor 4
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 11 2021
02 11 2021
Historique:
received:
10
12
2020
accepted:
18
10
2021
entrez:
3
11
2021
pubmed:
4
11
2021
medline:
22
1
2022
Statut:
epublish
Résumé
Activation of Toll-like receptors (TLR) 1/2 and 4 are central in inducing inflammation in sebocytes by regulating the expression of protein coding mRNAs, however the microRNA (miRNA) profile in response to TLR activation and thus the possible role of miRNAs in modulating sebocyte functions has not been elucidated. In this work we identified miR-146a to have the highest induction in the TLR1/2 and 4 activated SZ95 sebocytes and found that its increased levels led to the down-regulation of IL-8 secretion, decreased the chemoattractant potential and stimulated the proliferation of sebocytes. Assessing the gene expression profile of SZ95 sebocytes treated with a miR-146a inhibitor, the induction of GNG7 was one of the highest, while when cells were treated with a miR-146a mimic, the expression of GNG7 was down-regulated. These findings correlated with our in situ hybridization results, that compared with control, miR-146a showed an increased, while GNG7 a decreased expression in sebaceous glands of acne samples. Further studies revealed, that when inhibiting the levels of GNG7 in SZ95 sebocytes, cells increased their lipid content and decreased their proliferation. Our findings suggest, that miR-146a could be a potential player in acne pathogenesis by regulating inflammation, inducing proliferation and, through the indirect down-regulation of GNG7, promoting the lipid production of sebocytes.
Identifiants
pubmed: 34728702
doi: 10.1038/s41598-021-00907-1
pii: 10.1038/s41598-021-00907-1
pmc: PMC8563942
doi:
Substances chimiques
GNG7 protein, human
0
GTP-Binding Protein gamma Subunits
0
Lipids
0
MIRN146 microRNA, human
0
MicroRNAs
0
TLR1 protein, human
0
TLR2 protein, human
0
TLR4 protein, human
0
Toll-Like Receptor 1
0
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21510Subventions
Organisme : European Regional Development Fund
ID : GINOP-2.3.2-15-2016-00005
Organisme : European Regional Development Fund
ID : GINOP-2.3.2-15-2016-00005
Organisme : European Regional Development Fund
ID : GINOP-2.3.2-15-2016-00005
Organisme : Hungarian National Research, Development and Innovation Funds
ID : K-128250
Organisme : Hungarian National Research, Development and Innovation Funds
ID : FK-132296
Organisme : European Social Fund
ID : EFOP-3.6.1-16-2016-00022
Informations de copyright
© 2021. The Author(s).
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