Gene interactions and pathways from curated databases and text-mining
J Pharmacol Exp Ther 2006, PMID: 16682453

Hypoxia-inducible factor-1-dependent and -independent regulation of insulin-like growth factor-1-stimulated vascular endothelial growth factor secretion.

Slomiany, Mark G; Rosenzweig, Steven A

Hypoxia-induced stress plays a central role in retinal vascular disease and cancer. Increased hypoxia-inducible factor-1 alpha (Hif-1 alpha) expression leads to HIF-1 formation and the production of vascular endothelial growth factor (VEGF). Cytokines, including insulin-like growth factor-1 (IGF-1), also stimulate VEGF secretion. In this study, we examined the relationship between IGF-1 signaling, HIF-1 alpha protein turnover and VEGF secretion in the ARPE-19 retinal pigment epithelial cell line. Northern analysis revealed that IGF-1 stimulated Hif-1 alpha message expression, whereas the hypoxia-mimetic CoCl2 did not. CoCl2 treatment increased Hif-1 alpha protein accumulation to a greater extent than IGF-1 treatment. However, IGF-1 stimulated a more significant increase in VEGF secretion. IGF-1-stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR (mammalian target of rapamycin)-dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities. Analysis of VEGF promoter truncation mutants indicated that sensitivity to CoCl2 was hypoxia response element (HRE)-dependent with the region upstream of the HRE conferring IGF-1 sensitivity. In conclusion, IGF-1 regulates VEGF expression and secretion via HIF-1-dependent and -independent pathways.

Diseases/Pathways annotated by Medline MESH: Anoxia
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Text Mining Data

vascular endothelial growth factor → insulin-like growth factor-1: " Hypoxia-inducible factor-1 dependent and -independent regulation of insulin-like growth factor-1 stimulated vascular endothelial growth factor secretion "

VEGF → IGF-1: " However, IGF-1 stimulated a more significant increase in VEGF secretion "

VEGF → HIF-1: " IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities "

VEGF → PI3K/Akt/mTOR: " IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities "

VEGF → PI3K/Akt/mTOR: " IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities "

VEGF → IGF-1: " IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities "

VEGF → PI3K/Akt/mTOR: " IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities "

VEGF → IGF-1: " In conclusion, IGF-1 regulates VEGF expression and secretion via HIF-1 dependent and -independent pathways "

Manually curated Databases

No curated data.