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001-es BibID:BIBFORM098747
035-os BibID:(cikkazonosító)21510 (WOS)000714953500017 (Scopus)85118421272
Első szerző:Dull Katalin (molekuláris biológus, genetikus)
Cím: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 / Dull Katalin, Fazekas Fruzsina, Deák Dávid, Kovács Dóra, Póliska Szilárd, Szegedi Andrea, Zouboulis Christos C., Törőcsik Dániel
Dátum:2021
ISSN:2045-2322
Megjegyzések: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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 11 : 1 (2021), p. 1-13. -
További szerzők:Fazekas Fruzsina (1993-) (biológus) Deák Dávid Kovács Dóra (1988-) (Biológus) Póliska Szilárd (1978-) (biológus) Szegedi Andrea (1964-) (bőrgyógyász) Zouboulis, Christos C. (1960-) (bőrgyógyász) Töröcsik Dániel (1979-) (bőrgyógyász)
Pályázati támogatás:FK-132296
OTKA
K-128250
OTKA
GINOP-2.3.2-15-2016- 00005
GINOP
EFOP-3.6.1-16-2016-00022
EFOP
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM113710
035-os BibID:(cikkazonosító)3315 (WoS)001046283500001 (Scopus)85167680789
Első szerző:Kovács Dóra (Biológus)
Cím:Linoleic Acid Induced Changes in SZ95 Sebocytes-Comparison with Palmitic Acid and Arachidonic Acid / Dóra Kovács, Emanuela Camera, Szilárd Póliska, Alessia Cavallo, Miriam Maiellaro, Katalin Dull, Florian Gruber, Christos C. Zouboulis, Andrea Szegedi, Dániel Törőcsik
Dátum:2023
ISSN:2072-6643
Megjegyzések:Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Nutrients. - 15 : 15 (2023), p. 1-20. -
További szerzők:Camera, Emanuela Póliska Szilárd (1978-) (biológus) Cavallo, Alessia Maiellaro, Miriam Dull Katalin (1983-) (molekuláris biológus, genetikus) Gruber, Florian Zouboulis, Christos C. (1960-) (bőrgyógyász) Szegedi Andrea (1964-) (bőrgyógyász) Töröcsik Dániel (1979-) (bőrgyógyász)
Pályázati támogatás:FK-132296
OTKA
ANN 139589
OTKA
K-128250
OTKA
Italian Ministry of Health
Egyéb
FWF Austrian Science Fund; I 5627-B
Egyéb
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM081009
035-os BibID:(PMID)31562833 (WoS)000527223800107 (Scopus)85075431267
Első szerző:Kovács Dóra (Biológus)
Cím:Isotretinoin is indirectly effective in sebocytes / D. Kovács, K. Hegyi, A. Szegedi, D. Deák, Sz. Póliska, R. Rühl, C. C. Zouboulis, D. Törőcsik
Dátum:2020
ISSN:0007-0963 1365-2133
Megjegyzések:In a recently published research letter Burney et al. demonstrated that isotretinoin (13-cis-retinoic acid, 13CRA) induced acnegenic changes in SEB-1 cultured human sebocytes1 . However, Melnik et al., suggested that the observed changes may largely be influenced by the Simian virus (SV)-40 immortalization of the used cell line, which may inhibit the p53 pathway and together with 13CRA lead to changes, such as the down-regulation of the forkhead box O (FoxO) pathway. In contrast, they found that the FoxO pathway was upregulated in samples from patients receiving 13CRA treatment for 6 weeks.
Tárgyszavak:Orvostudományok Elméleti orvostudományok kutatási jelentés
folyóiratcikk
Megjelenés:British Journal of Dermatology. - 182 : 4 (2020), p. 1052-1054. -
További szerzők:Dull Katalin (1983-) (molekuláris biológus, genetikus) Szegedi Andrea (1964-) (bőrgyógyász) Deák Dávid Póliska Szilárd (1978-) (biológus) Rühl, Ralph (1969-) (vegyész) Zouboulis, Christos C. (1960-) (bőrgyógyász) Töröcsik Dániel (1979-) (bőrgyógyász)
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM108151
035-os BibID:(cikkazonosító)127 (Scopus)85146818567 (WoS)000916886200001
Első szerző:Somogyi Orsolya (klinikai laboratóriumi kutató)
Cím:New Data on the Features of Skin Barrier in Hidradenitis Suppurativa / Somogyi Orsolya, Dajnoki Zsolt, Szabó Lilla, Gáspár Krisztián, Hendrik Zoltán, Zouboulis Christos C., Dócs Klaudia, Szücs Péter, Dull Katalin, Törőcsik Dániel, Kapitány Anikó, Szegedi Andrea
Dátum:2023
ISSN:2227-9059
Megjegyzések:Hidradenitis suppurativa (HS) is a Th1/17-driven inflammatory skin disease of the apocrine gland-rich (AGR) skin regions, where keratinocytes seem to be the crucial drivers of the initial pathogenic steps. However, the possible role of permeability barrier alteration in activating keratinocytes during HS development has not been clarified. We compared the major permeability barrier elements of non-lesional HS (HS-NL; n = 10) and lesional HS (HS-L; n = 10) skin with healthy AGR regions (n = 10) via RT-qPCR and immunohistochemistry. Stratum corneum components related to cornified envelope formation, corneocyte desquamation and (corneo)desmosome organization were analyzed along with tight junction molecules and barrier alarmins. The permeability barrier function was also investigated with transepidermal water loss (TEWL) measurements (n = 16). Junction structures were also visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules changed significantly in HS-L skin versus control. At the protein level, the investigated molecules were similarly expressed in HS-NL and AGR skin. In HS-L skin, only slight changes were detected; however, differences did not show a unidirectional alteration, as KRT1 and KLK5 were detected in decreased levels, and KLK7, KRT6 and DSG1 in increased levels. No significant differences in TEWL or the expression of junction structures were assessed. Our findings suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
desmosome
hidradenitis suppurativa
keratinocyte
permeability barrier
tight junction
Megjelenés:Biomedicines. - 11 : 1 (2023), p. 1-12. -
További szerzők:Dajnoki Zsolt (1985-) (molekuláris biológus) Szabó Lilla (1993-) (molekuláris biológus) Gáspár Krisztián (1974-) (bőrgyógyász) Hendrik Zoltán (1986-) (orvos) Zouboulis, Christos C. (1960-) (bőrgyógyász) Dócs Klaudia (1989-) (orvos) Szűcs Péter (1974-) (kutatóorvos) Dull Katalin (1983-) (molekuláris biológus, genetikus) Töröcsik Dániel (1979-) (bőrgyógyász) Kapitány Anikó (1979-) (molekuláris biológus) Szegedi Andrea (1964-) (bőrgyógyász)
Pályázati támogatás:K 128250
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM094083
035-os BibID:(cikkazonosító)600017 (WoS)000652520500001 (Scopus)85106199263
Első szerző:Töröcsik Dániel (bőrgyógyász)
Cím:Epidermal Growth Factor Modulates Palmitic Acid-Induced Inflammatory and Lipid Signaling Pathways in SZ95 Sebocytes / Dániel Törőcsik, Fruzsina Fazekas, Szilárd Póliska, Andrea Gregus, Eszter Anna Janka, Katalin Dull, Andrea Szegedi, Christos C. Zouboulis, Dóra Kovács
Dátum:2021
ISSN:1664-3224
Megjegyzések:Epidermal growth factor (EGF) acts as a paracrine and autocrine mediator of cell proliferation and differentiation in various types of epithelial cells, such as sebocytes, which produce the lipid-rich sebum to moisturize the skin. However, sebum lipids via direct contact and by penetrating through the epidermis may have regulatory roles on epidermal and dermal cells as well. As EGF receptor (EGFR) is expressed throughout the proliferating and the lipid-producing layers of sebaceous glands (SGs) in healthy and acne-involved skin, we investigated the effect of EGF on SZ95 sebocytes and how it may alter the changes induced by palmitic acid (PA), a major sebum component with bioactive roles. We found that EGF is not only a potent stimulator of sebocyte proliferation, but also induces the secretion of interleukin (IL)6 and down-regulates the expression of genes involved in steroid and retinoid metabolism. Importantly, when applied in combination with PA, the PA-induced lipid accumulation was decreased and the cells secreted increased IL6 levels. Functional clustering of the differentially regulated genes in SZ95 sebocytes treated with EGF, PA or co-treated with EGF+PA further confirmed that EGF may be a potent inducer of hyperproliferative/inflammatory pathways (IL1 signaling), an effect being more pronounced in the presence of PA. However, while a group of inflammatory genes was up-regulated significantly in EGF+PA co-treated sebocytes, PA treatment in the absence of EGF, regulated genes only related to cell homeostasis. Meta-analysis of the gene expression profiles of whole acne tissue samples and EGF- and EGF+PA ?treated SZ95 sebocytes showed that the EGF+PA co-activation of sebocytes may also have implications in disease. Altogether, our results reveal that PA-induced lipid accumulation and inflammation can be modulated by EGF in sebocytes, which also highlights the need for system biological approaches to better understand sebaceous (immuno)biology.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Immunology. - 12 (2021), p. 1-16. -
További szerzők:Fazekas Fruzsina (1993-) (biológus) Póliska Szilárd (1978-) (biológus) Gregus Andrea (1980-) (biológus) Janka Eszter Anna (1989-) (bőrgyógyász, népegészségügyi szakember) Dull Katalin (1983-) (molekuláris biológus, genetikus) Szegedi Andrea (1964-) (bőrgyógyász) Zouboulis, Christos C. (1960-) (bőrgyógyász) Kovács Dóra (1988-) (Biológus)
Pályázati támogatás:FK-132296
OTKA
K-128250
OTKA
Bolyai ösztöndíj
MTA
ÚNKP-20-5
Egyéb
GINOP-2.3.2-15-2016-00005
GINOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM074734
035-os BibID:(cikkazonosító)e0198323 (WOS)000435802500016 (Scopus)85048863741
Első szerző:Töröcsik Dániel (bőrgyógyász)
Cím:Genome wide analysis of TLR1/2- and TLR4-activated SZ95 sebocytes reveals a complex immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands / Dániel Törőcsik, Dóra Kovács, Szilárd Póliska, Zita Szentkereszty-Kovács, Marianna Lovászi, Katalin Hegyi, Andrea Szegedi, Christos C. Zouboulis, Mona Ståhle
Dátum:2018
ISSN:1932-6203
Megjegyzések:Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in the development of acne. Still, there is only limited knowledge on their effect on sebocytes. In this work we performed global gene expression profile analysis with functional clustering of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide [LPS])-activated SZ95 sebocytes. Both TLR1/2- and 4-activation promoted inflammation in a similar manner already at an early time-point (6 hours), regulating genes involved in inflammation, wound healing and chemotaxis reflecting a more complex cytokine and chemokine regulation than previously known. Importantly, lipid metabolism, the primary feature of sebocytes, was affected at the level of gene expression only at a later time point (24 hours) indicating that sebocytes prioritize to exert a pro-inflammatory phenotype when confronted with a danger signal. Supporting the biological relevance of our results, a meta-analysis revealed that the genes showing the strongest up-regulation were also found up-regulated in acne. Of these genes, serum amyloid A 1/2 (SAA1/2) was confirmed to be a suitable protein marker for in vivo activated sebocytes, underlining their immune-competence, which is structurally defined within sebaceous glands of acne and rosacea skin samples. Altogether our findings demonstrate that sebocytes are not only positioned at the end point of inflammation but are actively involved in shaping the inflammatory response with putative diagnostic and therapeutic relevance.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Acne
Gene expression
Sebaceous glands
Inflammation
Gene regulation
Inflammatory diseases
Immune response
Lipid metabolism
Megjelenés:Plos One. - 13 : 6 (2018), p. 1-20. -
További szerzők:Kovács Dóra (1988-) (Biológus) Póliska Szilárd (1978-) (biológus) Szentkereszty-Kovács Zita (1988-) (orvos) Lovászi Marianna (1986-) (biológus) Dull Katalin (1983-) (molekuláris biológus, genetikus) Szegedi Andrea (1964-) (bőrgyógyász) Zouboulis, Christos C. (1960-) (bőrgyógyász) Ståhle, Mona
Pályázati támogatás:GINOP-2.3.2-15-2016-00005
GINOP
GINOP-2.3.2-15-2016-00050
GINOP
EFOP-3.6.1-16-2016-00022
EFOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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