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001-es BibID:	BIBFORM125810
Első szerző:	Dull Katalin (molekuláris biológus, genetikus)
Cím:	Sebum lipids selectively modulate gene expression in keratinocytes / Dull K., Ádám D., Póliska S., Aboud H., Szegedi A., Oláh A., Töröcsik D.
Dátum:	2024
ISSN:	0022-202X 1523-1747
Megjegyzések:	Changes in sebum quantity and composition have been reported in several skin diseases, suggesting a (patho) physiological role, but their effect on different cell types is not well characterized. Based on our previous findings that sebum lipids can penetrate the epidermis, this study aimed to investigate their effects on keratinocytes using pro-inflammatory (stearic acid and palmitic acid), anti- inflammatory lipids (linoleic acid and oleic acid) and squalene. In our experimental settings, HaCaT keratinocytes in subconfluent cultures with high proliferation rates (representing basal epidermal keratinocytes) and those in advanced differentiation in postconfluent cultures maintained under high Ca2+ concentrations (representing suprabasal epidermal layers) were treated with different sebum-composing lipids. The cell differentiation state was validated by measuring the expression of markers by RT-qPCR, and whole transcriptome analysis was performed using STRING platform. We found that keratinocytes exhibited differentiation-dependent unique gene expression patterns in response to the lipids. While squalene had the most significant effect on proliferating keratinocytes, palmitic and oleic acid treatments had a greater effect on differentiated cells. All lipids influenced cell proliferation and pathways related to cell cycle regulation. All treatments affected immune system-related pathways: in both differentiated and proliferating keratinocytes squalene, palmitic acid, and stearic acid treatments affected IL-17 signaling, cytokine signaling, interferon a/b, and TLR signaling. In this regard, the effect of stearic acid was the least pronounced. In conclusion, our results suggest that keratinocytes are able to selectively recognize and respond to the different lipids that make up sebum. Further characterization of the pathways involved may bring us closer to understanding the relevance of changes in sebum composition in different conditions such as acne and may provide the basis for improving sebum modulation therapies.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt folyóiratcikk sebocyte acne keratinocyte
Megjelenés:	Journal Of Investigative Dermatology. - 144 : 12 (2024), p. S264. -
További szerzők:	Ádám Dorottya (1991-) (molekuláris biológus) Póliska Szilárd (1978-) (biológus) Aboud, H. Szegedi Andrea (1964-) (bőrgyógyász) Oláh Attila (1984-) (élettanász) Töröcsik Dániel (1979-) (bőrgyógyász)
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001-es BibID:	BIBFORM083558
035-os BibID:	(WOS)000574374700009 (Scopus)85083011579
Első szerző:	Markovics Arnold (molekuláris biológus)
Cím:	GPR119 is a potent regulator of human sebocyte biology / Arnold Markovics, Ágnes Angyal, Kinga Fanni Tóth, Dorottya Ádám, Zsófia Pénzes, József Magi, Ágnes Pór, Ilona Kovács, Dániel Törőcsik, Christos C. Zouboulis, Tamás Bíró, Attila Oláh
Dátum:	2020
ISSN:	0022-202X 1523-1747
Megjegyzések:	We have previously shown that endocannabinoids promote sebaceous lipogenesis, and sebocytes are involved in the metabolism of the "endocannabinoid-like" substance oleoylethanolamide (OEA). OEA is an endogenous activator of GPR119, a recently de-orphanized receptor, which is currently being investigated as a promising anti-diabetic drug target. Thus, in the current study, we investigated the effects of OEA as well as the expression and role of GPR119 in human sebocytes. We found that OEA promoted differentiation of human SZ95 sebocytes (elevated lipogenesis, enhanced granulation, and the induction of early apoptotic events), and it switched the cells to a pro-inflammatory phenotype (increased expression and release of several pro-inflammatory cytokines). Moreover, we could also demonstrate that GPR119 was expressed in human sebocytes, and its siRNA-mediated gene silencing suppressed OEA-induced sebaceous lipogenesis, which was mediated via JNK, ERK1/2, Akt/PKB, and CREB activation. Finally, our pilot data demonstrated that GPR119 was down-regulated in sebaceous glands of acne patients, arguing that GPR119 signaling may indeed be disturbed in acne. Collectively, our findings introduce the OEA?GPR119 signaling as a new positive regulator of sebocyte differentiation, and highlight the possibility that dysregulation of this pathway may contribute to the development of seborrhea and acne.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk GPR119 acne sebocyte oleoylethanolamide seborrhea inflammation
Megjelenés:	Journal of Investigative Dermatology. - 140 : 10 (2020), p. 1909-1918. -
További szerzők:	Angyal Ágnes (1987-) (molekuláris biológus) Tóth Kinga Fanni (1992-) (molekuláris biológus, élettanász) Ádám Dorottya (1991-) (molekuláris biológus) Pénzes Zsófia (1992-) (klinikai laboratóriumi kutató) Magi József Pór Ágnes Kovács Ilona (1965-) (patológus) Töröcsik Dániel (1979-) (bőrgyógyász) Zouboulis, Christos C. (1960-) (bőrgyógyász) Bíró Tamás (1968-) (élettanász) Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	120552 OTKA 121360 OTKA 125055 OTKA Bolyai János Kutatási Ösztöndíj MTA GINOP-2.3.2-15-2016-00050 GINOP Galderma Acne and Rosacea Basic Research Award Egyéb ÚNKP-19-4-DE-287 Egyéb ÚNKP-19-4-DE-15 Egyéb ÚNKP-19-3-I-DE-141 Egyéb EFOP-3.6.3-VEKOP-16-2017-00009 EFOP
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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