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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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