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001-es BibID:	BIBFORM116424
Első szerző:	Ádám Dorottya (molekuláris biológus)
Cím:	The TRPM5 antagonist TPPO increases sebaceous lipogenesis and exerts pro-inflammatory effects via activation of Akt and p38 MAPK cascades / Ádám D., Arany J., Pető O., Tóth B. I., Zouboulis C. C., Oláh A.
Dátum:	2023
ISSN:	0022-202X 1523-1747
Megjegyzések:	We have previously shown that transient receptor potential vanilloid (TRPV)-1, -3, and -4 ion channels are negative regulators of sebaceous lipogenesis. Moreover, the transient receptor potential melastatin 5 (TRPM5) was recently demonstrated to be expressed in human hair follicles, where its homeostatic activity appeared to promote the anagen phase (PMID: 33773986). Because the immunofluorescent images published in said article indicated that sebaceous glands also exhibited TRPM5 positivity, TRPM5 modulators administered with the intention of influencing hair growth may also have an unintended impact on sebaceous gland functions. Thus, we aimed to investigate the effects of TRPM5 modulators on human SZ95 sebocytes. SZ95 sebocytes were treated with TRPM5 modulators (activators: 2,5-dimethylpyrazine [DMP], 2-heptanone [HEP]; antagonist: triphenylphosphine oxide [TPPO]), and viability (MTT-assay), lipid synthesis (Nile Red labeling), gene expression (Q-PCR, western blot), mediator release (ELISA), as well as time-dependent activation of relevant second messenger pathways (phosphokinase array) were monitored. Expression of TRPM5 was knocked down by siRNA-transfection. Expression of TRPM5 was found to be around detection limit at the mRNA level, and western blotting did not produce bands at the predicted molecular weights either. Because siRNA-mediated silencing of TRPM5 failed to alter the intensity of the apparently nonspecific bands, we concluded that TRPM5 is most likely not expressed in human sebocytes. Furthermore, we found that the activators did not influence viability and lipid synthesis. Interestingly TPPO promoted sebaceous lipogenesis, and increased interleukin (IL)-6 expression and release. Phosphokinase array revealed the time-dependent activation of several kinase cascades in response to TPPO-treatment. Using pharmacological inhibitors, we could demonstrate that lipogenic effect of TPPO was mediated via the activation of the Akt1/2/3 and p38 MAPK. We concluded that the use of TPPO is likely to influence sebaceous gland biology via activating certain cellular off-targets.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt folyóiratcikk TRPM5 sebocyte TPPO acne dry skin
Megjelenés:	Journal Of Investigative Dermatology. - 143 : 11 (2023), p. S354. -
További szerzők:	Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Pető O. Tóth István Balázs (1978-) (élettanász) Zouboulis, Christos C. (1960-) (bőrgyógyász) Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	EFOP-3.6.3-VEKOP-16-2017-00009 EFOP EFOP-3.6.1-16-2016-00022 EFOP 134235 OTKA ÚNKP-23-5-DE-477 Egyéb János Bolyai Research Scholarship MTA
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001-es BibID:	BIBFORM101339
035-os BibID:	(cikkazonosító)4140 (scopus)85127787477 (wos)000786332700001
Első szerző:	Ádám Dorottya (molekuláris biológus)
Cím:	Opioidergic Signaling : a Neglected, Yet Potentially Important Player in Atopic Dermatitis / Dorottya Ádám, József Arany, Kinga Fanni Tóth, Balázs István Tóth, Attila Gábor Szöllősi, Attila Oláh
Dátum:	2022
ISSN:	1661-6596 1422-0067
Megjegyzések:	Atopic dermatitis (AD) is one of the most common skin diseases, the prevalence of which is es-pecially high among children. Although our understanding about its pathogenesis has substan-tially grown in recent years, and hence, several novel therapeutic targets have been successfully exploited in the management of the disease, we still lack curative treatments for it. Thus, there is an unmet societal demand to identify further details of its pathogenesis to thereby pave the way for novel therapeutic approaches with favorable side effect profiles. It is commonly accepted that dysfunction of the complex cutaneous barrier plays a central role in the development of AD; therefore, the signaling pathways involved in the regulation of this quite complex process are likely to be involved in the pathogenesis of the disease and can provide novel, promising, yet unexplored therapeutic targets. Thus, in the current review, we aim to summarize the available potentially AD-relevant data regarding one such signaling pathway, namely cutaneous opi-oidergic signaling.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk atopic dermatitis (AD) cutaneous barrier [delta]-opioid receptor (DOR) inflammation itch [delta]-opioid receptor (KOR) keratinocyte mast cell [delta]-opioid receptor (MOR) nociceptin/orphanin FQ (NOP) receptor opioid skin
Megjelenés:	International Journal Of Molecular Sciences. - 23 : 8 (2022), p. 4140. -
További szerzők:	Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Tóth Kinga Fanni (1992-) (molekuláris biológus, élettanász) Tóth István Balázs (1978-) (élettanász) Szöllősi Attila Gábor (1982-) (élettanász) Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00026 GINOP NKFIH 120187 Egyéb NKFIH 134235 Egyéb NKFIH 134725 Egyéb NKFIH 134993 Egyéb EFOP-3.6.3-VEKOP-16-2017-00009 EFOP Bolyai János Kutatási Ösztöndíj (BO/00660/21/5) MTA Bolyai János Kutatási Ösztöndíj (BO/00905/19/5) MTA ÚNKP-21-5-DE-465 Egyéb ÚNKP-21-5-DE-491 Egyéb
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