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001-es BibID:	BIBFORM064981
Első szerző:	Szatmári-Tóth Mária (molekuláris biológus)
Cím:	Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration / Szatmári-Tóth Mária, Kristóf Endre, Veréb Zoltán, Saeed Akhtar, Facskó Andrea, Fésüs László, Anu Kauppinen, Kai Kaarniranta, Goran Petrovski
Dátum:	2016
ISSN:	2041-4889
Megjegyzések:	Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3 II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, while sorting out the GFP-LC3 positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modelling of AMD pathogenesis.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban autofágia, fagicitózis, makrofágok, triamcinolone, gyulladás, időskori makula degeneráció
Megjelenés:	Cell Death & Disease 7 : 9 (2016), p. e2367. -
További szerzők:	Kristóf Endre (1987-) (általános orvos) Veréb Zoltán (1980-) (immunológus, mikrobiológus, molekuláris biológus) Akhtar, Saeed (1949-) (molekuláris biológus) Facskó Andrea (1953-) (szemész) Fésüs László (1947-) (orvos biokémikus) Kauppinen, Anu (1977-) (sejtbiológus) Kaarniranta, Kai (1972-) (szemész szakorvos) Petrovski, Goran (1975-) (szemész szakorvos)
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001-es BibID:	BIBFORM049100
Első szerző:	Veréb Zoltán (immunológus, mikrobiológus, molekuláris biológus)
Cím:	Comparison of upstream regulators in human ex vivo cultured cornea limbal epithelial stem cells and differentiated corneal epithelial cells / Zoltán Veréb, Réka Albert, Szilárd Póliska, Ole Kristoffer Olstad, Saeed Akhtar, Morten C. Moe, Goran Petrovski
Dátum:	2013
ISSN:	1471-2164
Megjegyzések:	BACKGROUND:The surface of the human eye is covered by corneal epithelial cells (CECs) which regenerate from a small population of limbal epithelial stem cells (LESCs). Cell therapy with LESCs is a non-penetrating treatment for preventing blindness due to LESC deficiency or dysfunction. Our aim was to identify new putative molecular markers and upstream regulators in the LESCs and associated molecular pathways.RESULTS:Genome-wide microarray transcriptional profiling was used to compare LESCs to differentiated human CECs. Ingenuity-based pathway analysis was applied to identify upstream regulators and pathways specific to LESCs. ELISA and flow cytometry were used to measure secreted and surface expressed proteins, respectively. More than 2 fold increase and decrease in expression could be found in 1830 genes between the two cell types. A number of molecules functioning in cellular movement (381), proliferation (567), development (552), death and survival (520), and cell-to-cell signaling (290) were detected having top biological functions in LESCs and several of these were confirmed by flow cytometric surface protein analysis. Custom-selected gene groups related to stemness, differentiation, cell adhesion, cytokines and growth factors as well as angiogenesis could be analyzed. The results show that LESCs play a key role not only in epithelial differentiation and tissue repair, but also in controlling angiogenesis and extracellular matrix integrity. Some pro-inflammatory cytokines were found to be important in stemness-, differentiation- and angiogenesis-related biological functions: IL-6 and IL-8 participated in most of these biological pathways as validated by their secretion from LESC cultures.CONCLUSIONS:The gene and molecular pathways may provide a more specific understanding of the signaling molecules associated with LESCs, therefore, help better identify and use these cells in the treatment of ocular surface diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Limbal epithelial stem cells Corneal epithelial cells Gene array Upstream regulators Cytokines Cell adhesion IL-6 IL-8 Angiogenesis
Megjelenés:	BMC Genomics. - 14 : 1 (2013), p. [1-33]. -
További szerzők:	Albert Réka (1986-) Póliska Szilárd (1978-) (biológus) Olstad, Ole Kristoffer Akhtar, Saeed (1949-) (molekuláris biológus) Moe, Morten C. Petrovski, Goran (1975-) (orvos)
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