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001-es BibID:	BIBFORM118666
035-os BibID:	(Scopus)85184251918 (WOS)001155051600001
Első szerző:	Ababneh, Haneen Muntasir
Cím:	High glucose promotes osteogenic differentiation of human lens epithelial cells through hypoxia-inducible factor (HIF) activation / Haneen Ababneh, Enikő Balogh, Dávid Máté Csiki, Gréta Lente, Ferenc Fenyvesi, Andrea Tóth, Viktória Jeney
Dátum:	2024
ISSN:	0021-9541 1097-4652
Megjegyzések:	Cataract, a leading cause of blindness, is characterised by lens opacification. Type 2 diabetes is associated with a two- to fivefold higher prevalence of cataracts. The risk of cataract formation increases with the duration of diabetes and the severity of hyperglycaemia. Hydroxyapatite deposition is present in cataractous lenses that could be the consequence of osteogenic differentiation and calcification of lens epithelial cells (LECs). We hypothesised that hyperglycaemia might promote the osteogenic differentiation of human LECs (HuLECs). Osteogenic medium (OM) containing excess phosphate and calcium with normal (1 g/L) or high (4.5 g/L) glucose was used to induce HuLEC calcification. High glucose accelerated and intensified OM-induced calcification of HuLECs, which was accompanied by hyperglycaemia-induced upregulation of the osteogenic markers Runx2, Sox9, alkaline phosphatase and osteocalcin, as well as nuclear translocation of Runx2. High glucose-induced calcification was abolished in Runx2-deficient HuLECs. Additionally, high glucose stabilised the regulatory alpha subunits of hypoxia-inducible factor 1 (HIF-1), triggered nuclear translocation of HIF-1? and increased the expression of HIF-1 target genes. Gene silencing of HIF-1? or HIF-2? attenuated hyperglycaemia-induced calcification of HuLECs, while hypoxia mimetics (desferrioxamine, CoCl2) enhanced calcification of HuLECs under normal glucose conditions. Overall, this study suggests that high glucose promotes HuLEC calcification via Runx2 and the activation of the HIF-1 signalling pathway. These findings may provide new insights into the pathogenesis of diabetic cataracts, shedding light on potential factors for intervention to treat this sight-threatening condition.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk cataract hyperglycaemia hypoxia-inducible factor (HIF) lens calcification lens epithelial cell osteogenic differentiation
Megjelenés:	Journal Of Cellular Physiology. - [Epub ahead of print] (2024). -
További szerzők:	Balogh Enikő (1987-) (molekuláris biológus) Csiki Dávid Máté (1993-) (biomérnök) Lente Gréta (1994-) (klinikai laboratóriumi kuatató) Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Tóth Andrea (1992-) (molekuláris biológus) Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:	NKFIH K146669 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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