Changes of glycosphingolipid profiles in human bronchial epithelial cells and extracellular vesicles during gradual benzo[a]pyrene-induced epithelial-mesenchymal transition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F23%3AN0000109" target="_blank" >RIV/00027162:_____/23:N0000109 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Changes of glycosphingolipid profiles in human bronchial epithelial cells and extracellular vesicles during gradual benzo[a]pyrene-induced epithelial-mesenchymal transition

Popis výsledku v původním jazyce

Poster. In: 12th International Ceramide Conference, Charleston, SC, USA, April 16-20, 2023, p. 54. Benzo[a]pyrene (BaP), a well-known human carcinogens, has been primarily studied as tumor initiating compound, while its effects on tumor promotion and progression are not well characterized. Here, we assessed the multi-step process of epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (HBEC-12KT) exposed for 12 weeks by non-cytotoxic concentration of BaP, with focus on changes in glycosphingolipid (GSL) composition. After 2-week exposure, levels of GM3, GM1a, Gb3, GA2/Lc3 and sulfatide were increased; the content of Gb3, GA2/Lc3, sulfatide, GD3 and GD1a/GD1b increased after 8 weeks. In transformed mesenchymal-like cells, Gb3, GDA2/Lc3, GD3 and GD1a/GD1b increased, while GM3, GM1a and sulfatide concentrations were reduced. Changes in expression of genes linked with GSL biosynthesis only partly corresponded with modulations of intracellular GSL concentrations. We observed increased expression of Gb3 and GD3 synthases in the fully transformed HBEC-12KT-B1 cells, but not in early (2-weeks) and late (8-weeks) intermediate EMT periods. Other GSL synthases and hydrolases were mostly downregulated. We then performed GSL analyses in exosomes and larger microvesicles isolated from control and BaP-treated cells. The cellular alterations of GSL content were reflected in both types of extracellular vesicles. In parallel, we also determined transcriptional and phenotypical alterations associated with a gradual BaP-induced transition into mesenchymal-like cells. We tentatively identified AHR, CDKN1A and SERPINB2 (responsible for cell cycle delay and early morphological changes at 2-week exposure), EMT-related transcription factors ZEB1 and ZEB2 (upregulated only after 8 weeks, altogether with induction of cell migration) and several proinflammatory factors as potential regulators of early and late intermediate phases of EMT induced by BaP. We aim to further seek links between candidate genes responsible for gradual BaP-induced EMT and GSL alterations, as well as potential roles of GSLs during the chemical-induced multi-step EMT process.

Název v anglickém jazyce

Changes of glycosphingolipid profiles in human bronchial epithelial cells and extracellular vesicles during gradual benzo[a]pyrene-induced epithelial-mesenchymal transition

Popis výsledku anglicky

Poster. In: 12th International Ceramide Conference, Charleston, SC, USA, April 16-20, 2023, p. 54. Benzo[a]pyrene (BaP), a well-known human carcinogens, has been primarily studied as tumor initiating compound, while its effects on tumor promotion and progression are not well characterized. Here, we assessed the multi-step process of epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (HBEC-12KT) exposed for 12 weeks by non-cytotoxic concentration of BaP, with focus on changes in glycosphingolipid (GSL) composition. After 2-week exposure, levels of GM3, GM1a, Gb3, GA2/Lc3 and sulfatide were increased; the content of Gb3, GA2/Lc3, sulfatide, GD3 and GD1a/GD1b increased after 8 weeks. In transformed mesenchymal-like cells, Gb3, GDA2/Lc3, GD3 and GD1a/GD1b increased, while GM3, GM1a and sulfatide concentrations were reduced. Changes in expression of genes linked with GSL biosynthesis only partly corresponded with modulations of intracellular GSL concentrations. We observed increased expression of Gb3 and GD3 synthases in the fully transformed HBEC-12KT-B1 cells, but not in early (2-weeks) and late (8-weeks) intermediate EMT periods. Other GSL synthases and hydrolases were mostly downregulated. We then performed GSL analyses in exosomes and larger microvesicles isolated from control and BaP-treated cells. The cellular alterations of GSL content were reflected in both types of extracellular vesicles. In parallel, we also determined transcriptional and phenotypical alterations associated with a gradual BaP-induced transition into mesenchymal-like cells. We tentatively identified AHR, CDKN1A and SERPINB2 (responsible for cell cycle delay and early morphological changes at 2-week exposure), EMT-related transcription factors ZEB1 and ZEB2 (upregulated only after 8 weeks, altogether with induction of cell migration) and several proinflammatory factors as potential regulators of early and late intermediate phases of EMT induced by BaP. We aim to further seek links between candidate genes responsible for gradual BaP-induced EMT and GSL alterations, as well as potential roles of GSLs during the chemical-induced multi-step EMT process.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA21-00533S" target="_blank" >GA21-00533S: Nekonvenční environmentální ligandy Ah receptoru a jejich komplexní účinky in vitro</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů