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

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 b...

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Vydané v:Scientific reports Ročník 11; číslo 1; s. 21510 - 13
Hlavní autori: Dull, Katalin, Fazekas, Fruzsina, Deák, Dávid, Kovács, Dóra, Póliska, Szilárd, Szegedi, Andrea, Zouboulis, Christos C., Törőcsik, Dániel
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 02.11.2021
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Acne
Acne Vulgaris - genetics
Acne Vulgaris - immunology
Acne Vulgaris - metabolism
Acne Vulgaris - pathology
Adult
Case-Control Studies
Cell Proliferation
Cells, Cultured
Down-regulation
Gene expression
Gene Expression Regulation
GTP-Binding Protein gamma Subunits - genetics
GTP-Binding Protein gamma Subunits - metabolism
Humanities and Social Sciences
Humans
Hybridization
Inflammation
Inflammation - genetics
Inflammation - immunology
Inflammation - metabolism
Inflammation - pathology
Interleukin 8
Lipids
Lipids - analysis
Lipogenesis
Male
MicroRNAs
MicroRNAs - genetics
miRNA
multidisciplinary
RNA-Seq
Science
Science (multidisciplinary)
Sebaceous gland
Sebaceous Glands - immunology
Sebaceous Glands - metabolism
Sebaceous Glands - pathology
TLR1 protein
Toll-Like Receptor 1 - genetics
Toll-Like Receptor 1 - metabolism
Toll-Like Receptor 2 - genetics
Toll-Like Receptor 2 - metabolism
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - metabolism
Toll-like receptors
ISSN:2045-2322, 2045-2322
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-00907-1