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001-es BibID:	BIBFORM059157
035-os BibID:	(cikkazonosító)e0131141
Első szerző:	Boros Gábor (biokémikus, molekuláris biológus)
Cím:	Identification of Cyclobutane Pyrimidine Dimer-Responsive Genes Using UVB-Irradiated Human Keratinocytes Transfected with In Vitro-Synthesized Photolyase mRNA / Gábor Boros, Edit Miko, Hiromi Muramatsu, Drew Weissman, Eszter Emri, Gijsbertus T. J. van der Horst, Andrea Szegedi, Irén Horkay, Gabriella Emri, Katalin Karikó, Éva Remenyik
Dátum:	2015
ISSN:	1932-6203
Megjegyzések:	Major biological effects of UVB are attributed to cyclobutane pyrimidine dimers (CPDs), the most common photolesions formed on DNA. To investigate the contribution of CPDs to UVB-induced changes of gene expression, a model system was established by transfecting keratinocytes with pseudouridine-modified mRNA (?-mRNA) encoding CPD-photolyase. Microarray analyses of this model system demonstrated that more than 50% of the gene expression altered by UVB was mediated by CPD photolesions. Functional classification of the gene targets revealed strong effects of CPDs on the regulation of the cell cycle and transcriptional machineries. To confirm the microarray data, cell cycle-regulatory genes, CCNE1 and CDKN2B that were induced exclusively by CPDs were selected for further investigation. Following UVB irradiation, expression of these genes increased significantly at both mRNA and protein levels, but not in cells transfected with CPD-photolyase ?-mRNA and exposed to photoreactivating light. Treatment of cells with inhibitors of c-Jun N-terminal kinase (JNK) blocked the UVB-dependent upregulation of both genes suggesting a role for JNK in relaying the signal of UVB-induced CPDs into transcriptional responses. Thus, photolyase mRNA-based experimental platform demonstrates CPD-dependent and -independent events of UVB-induced cellular responses, and, as such, has the potential to identify novel molecular targets for treatment of UVB-mediated skin diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Plos One. - 10 : 6 (2015), p. 1-19. -
További szerzők:	Mikó Edit (1980-) (biológus) Muramatsu, Hiromi Weissman, Drew Emri Eszter (1985-) (Ph.D hallgató) van der Horst, Gijsbertus T. J. Szegedi Andrea (1964-) (bőrgyógyász) Horkay Irén (1938-) (bőrgyógyász, labor szakorvos, kozmetológus) Emri Gabriella (1972-) (bőrgyógyász, allergológus, onkológus) Karikó Katalin (1955-) (biológus, biokémikus) Remenyik Éva (1956-) (bőrgyógyász)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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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
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