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001-es BibID:	BIBFORM129513
035-os BibID:	(WoS)001482469000001 (Scopus)105004690504
Első szerző:	Ádám Dorottya (molekuláris biológus)
Cím:	The TRPM5 antagonist triphenylphosphine oxide (TPPO) increases sebaceous lipogenesis and modulates immune phenotype of human sebocytes in a TRPM5-independent manner / Ádám Dorottya, Arany József, Tóth Kinga Fanni, Pető Orsolya, Nyitrai Tamara, Tóth István Balázs, Póliska Szilárd, Christos C. Zouboulis, Oláh Attila
Dátum:	2025
ISSN:	0906-6705
Megjegyzések:	Transient receptor potential melastatin 5 (TRPM5) ion channel is expressed in human hair follicles, where its spontaneous activity contributes to the maintenance of the growing, anagen phase of the hair cycle. Because adjacent sebaceous glands also exhibited TRPM5 immunopositivity, topically applied TRPM5 modulators administered to influence hair growth may also affect sebaceous glands. Hence, we aimed to assess expression of TRPM5 as well as effects of TRPM5 modulators (activators: 2,5-dimethylpyrazine, 2-heptanone; antagonist: triphenylphosphine oxide [TPPO]) on human SZ95 sebocytes, i.e., on the best available in vitro model to study human sebaceous glands. First, using complementary methods (RNA-Seq, RT-qPCR, western blot, siRNA-mediated gene silencing, as well as fluorescent Na+- [SBFI AM] and Ca2+-measurements [Fura-2 AM]), we found that TRPM5 is not expressed in human sebocytes in a functionally active form. Importantly, while non-cytotoxic (MTT-assay) concentrations of the activators were ineffective, TPPO promoted sebaceous lipogenesis (Nile Red labeling). This effect was TRPM5-independent and was found to be mediated in an Akt- and epidermal growth factor receptor (EGFR)-dependent manner, most likely via the Akt-induced up-regulation of diacylglycerol O-acyltransferase (DGAT)-2. Moreover, TPPO up-regulated interleukin (IL)-6 in an EGFR- and p38? MAPK-dependent manner (RT-qPCR), while it decreased release of IL-8 (ELISA), and down-regulated additional pro-inflammatory cytokines (chemokine (C-X-C motif) ligand [CXCL]-1, CXCL2, CXCL6, colony-stimulating factor 2, IL-32; RNA-Seq). Collectively, specific TRPM5 modulators are unlikely to exert direct sebaceous gland-related side effects, while safe TPPO analogues may induce beneficial moderate lipogenic and anti-inflammatory effects in dry skin dermatoses.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk acne dry skin inflammation sebum sebocyte TPPO
Megjelenés:	Experimental Dermatology. - 34 : 5 (2025), p. 1-13. -
További szerzők:	Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Tóth Kinga Fanni (1992-) (molekuláris biológus, élettanász) Pető Orsolya Nyitrai Tamara (1999-) (molekuláris biológus) Tóth István Balázs (1978-) (élettanász) Póliska Szilárd (1978-) (biológus) Zouboulis, Christos C. (1960-) (bőrgyógyász) Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	NKFIH 134235 Egyéb NKFIH 134725 Egyéb EFOP-3.6.3-VEKOP-16-2017-00009 EFOP EFOP-3.6.1-16-2016-00022 EFOP GINOP-2.3.2-15-2016-00050 GINOP BO/00660/21/5 MTA ÚNKP-22-5-DE-427 Egyéb ÚNKP-23-5-DE-477 Egyéb TKP2021-NKTA-34 Egyéb "Momentum" proof-of-concept fund (Faculty of Medicine, University of Debrecen) Egyéb
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001-es BibID:	BIBFORM125809
Első szerző:	Ádám Dorottya (molekuláris biológus)
Cím:	The TRPM5 antagonist triphenylphosphine oxide increases sebaceous lipogenesis and modulates immune phenotype of human sebocytes in a TRPM5-independent manner / Ádám D., Arany J., Tóth K. F., Petö O., Nyitrai T., Tóth B. I., Póliska S., Zouboulis C. C., Oláh A.
Dátum:	2024
Megjegyzések:	It has recently been shown that transient receptor potential melastatin 5 (TRPM5) ion channels contributed to the maintenance of the anagen phase of the hair cycle. Because adjacent sebaceous glands also exhibited TRPM5 immunopositivity, topically applied TRPM5 modulators administered with the intention to influence hair growth may also affect sebaceous glands (SGs). Hence, we aimed to assess expression of TRPM5 as well as effects of 2 agonists and 1 antagonist (triphenylphosphine oxide [TPPO]) of TRPM5 on human SZ95 sebocytes. First, using complementary methods (RNA-Seq, RT-qPCR, western blot, siRNA-mediated gene silencing, fluorescent Na+- and Ca2+-measurements), we found that TRPM5 is not expressed in human sebocytes in a functionally active form.While non- cytotoxic (MTT-assay) concentrations of the activators were ineffective, TPPO promoted sebaceous lipogenesis (Nile Red). This effect was TRPM5-independent and was found to be mediated in an Akt- and epidermal growth factor receptor (EGFR)-dependent manner, most likely via the Akt-induced up-regulation of diacylglycerol O-acyltransferase-2. Moreover, TPPO up-regulated interleukin (IL)-6 in an EGFR- and p38a MAPKdependent manner (RT-qPCR), while it decreased release of IL-8 (ELISA), and it down-regulated additional pro-inflammatory cytokines (chemokine (C-X-C motif) ligand [CXCL]-1, CXCL2, CXCL6, colony-stimulating factor 2, IL-32). Collectively, specific TRPM5 modulators are unlikely to exert direct SG-related side effects, while safe TPPO analogues may induce beneficial moderate lipogenic and anti-inflammatory effects in dry skin dermatoses.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt folyóiratcikk sebocyte acne TRPM5 TPPO
Megjelenés:	The Journal of Investigative Dermatology. - 144 : 12_Suppl (2024), p. S313. -
További szerzők:	Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Tóth Kinga Fanni (1992-) (molekuláris biológus, élettanász) Pető Orsolya Nyitrai Tamara (1999-) (molekuláris biológus) Tóth István Balázs (1978-) (élettanász) Póliska Szilárd (1978-) (biológus) Zouboulis, Christos C. (1960-) (bőrgyógyász) Oláh Attila (1984-) (élettanász)
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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 Orsolya 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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