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

Abstract 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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Katalin Dull, Fruzsina Fazekas, Dávid Deák, Dóra Kovács, Szilárd Póliska, Andrea Szegedi, Christos C. Zouboulis, Dániel Törőcsik
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/24d3d019ee154af4a9038e1941abd4dc
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:24d3d019ee154af4a9038e1941abd4dc
record_format dspace
spelling oai:doaj.org-article:24d3d019ee154af4a9038e1941abd4dc2021-11-08T10:54:46ZmiR-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 sebocytes10.1038/s41598-021-00907-12045-2322https://doaj.org/article/24d3d019ee154af4a9038e1941abd4dc2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00907-1https://doaj.org/toc/2045-2322Abstract 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.Katalin DullFruzsina FazekasDávid DeákDóra KovácsSzilárd PóliskaAndrea SzegediChristos C. ZouboulisDániel TörőcsikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Katalin Dull
Fruzsina Fazekas
Dávid Deák
Dóra Kovács
Szilárd Póliska
Andrea Szegedi
Christos C. Zouboulis
Dániel Törőcsik
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
description Abstract 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.
format article
author Katalin Dull
Fruzsina Fazekas
Dávid Deák
Dóra Kovács
Szilárd Póliska
Andrea Szegedi
Christos C. Zouboulis
Dániel Törőcsik
author_facet Katalin Dull
Fruzsina Fazekas
Dávid Deák
Dóra Kovács
Szilárd Póliska
Andrea Szegedi
Christos C. Zouboulis
Dániel Törőcsik
author_sort Katalin Dull
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/24d3d019ee154af4a9038e1941abd4dc
work_keys_str_mv AT katalindull mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT fruzsinafazekas mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT daviddeak mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT dorakovacs mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT szilardpoliska mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT andreaszegedi mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT christosczouboulis mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
AT danieltorocsik mir146amodulatestlr12and4inducedinflammationandlinksitwithproliferationandlipidproductionviatheindirectregulationofgng7inhumansz95sebocytes
_version_ 1718442504400928768