Hypoxia induced expression of histone lysine demethylases: implications in oxygen-dependent retinal neovascular diseases.
Biochem Biophys Res Commun
; 415(2): 373-7, 2011 Nov 18.
Article
en En
| MEDLINE
| ID: mdl-22037463
ABSTRACT
Hypoxia inducible factor (HIF) plays a critical role in cellular adaptation to hypoxia by regulating the expression of essential genes. Pathological activation of this pathway leads to the expression of pro-angiogenic factors during the neovascularization in cancer and retinal diseases. Little is known about the epigenetic regulations during HIF-mediated transcription and activation of pro-angiogenic genes in oxygen-dependent retinal diseases. Here, we show that hypoxia induces the expression of a number of histone lysine demethylases (KDMs) in retinal pigment epithelial cells. Moreover, we show that the expression of pro-angiogenic genes (ADM, GDF15, HMOX1, SERPE1 and SERPB8) is dependent on KDMs under hypoxic conditions. Further, treating the cells with a general KDM inhibitor blocks the expression of these pro-angiogenic genes. Results from these studies identify a new layer of epigenetic transcription regulation under hypoxic conditions and suggest that specific inhibitors of KDMs such as JMJD1A can be a new therapeutic approach to treat diseases caused by the hypoxia induced neovascularization in cancer and retinal diseases.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oxígeno
/
Neovascularización Retiniana
/
Epigénesis Genética
/
Epitelio Pigmentado de la Retina
/
Histona Demetilasas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos