NYMC Faculty Publications
Elevated Cell Proliferation and VEGF Production by High-Glucose Conditions in Müller Cells Involve XIAP
Author Type(s)
Faculty
DOI
10.1038/eye.2013.158
Journal Title
Eye
First Page
1299
Last Page
1307
Document Type
Article
Publication Date
11-1-2013
Department
Medicine
Abstract
PURPOSE: Müller cells have important roles in the pathogenesis of diabetic retinopathy by promoting cell proliferation and inducing the production of vascular endothelial growth factor (VEGF) under hyperglycemic conditions. The objective of this study was to determine the potential mechanism of Müller cell proliferation and VEGF production due to high-glucose conditions.
METHODS: Primary cultured rat Müller cells were incubated with medium containing variable concentrations of glucose and/or embelin, a specific inhibitor of X-linked inhibitor of apoptosis protein (XIAP), for 72 h. The proliferation of Müller cells was assessed by the MTT assay. The expression and/or phosphorylation of 146 proteins were assessed using protein pathway array.
RESULTS: High concentrations of glucose-induced Müller cell proliferation and altered expression and/or phosphorylation of 47 proteins that have been identified to have key roles in several important signaling pathways (XIAP, VEGF, HIF1α, NFκB, etc) and are involved in the regulation of cell survival, proliferation, or apoptosis. However, Müller cell alterations induced by high-glucose conditions were counteracted by the XIAP inhibitor embelin, and 26 proteins/phosphorylations (out of 47) were restored to their normal levels. Nine proteins, including NFκB p65, p-p38, tumor necrosis factor-α, urokinase-type plasminogen activator, CREB, IL-1β, HCAM, estrogen receptor-α, and p-Stat3, were involved in regulatory networks between XIAP and VEGF.
CONCLUSIONS: The current study suggests that XIAP may be a potential regulator that can mediate a series of pathological changes induced by high-glucose conditions in Müller cells. Therefore, embelin could be a potential agent for the prevention and treatment of diabetic retinopathy.
Recommended Citation
Sun, Y., Wang, D., Ye, F., Hu, D., Liu, X., Zhang, L., Gao, L., Song, E., & Zhang, D. (2013). Elevated Cell Proliferation and VEGF Production by High-Glucose Conditions in Müller Cells Involve XIAP. Eye, 27 (11), 1299-1307. https://doi.org/10.1038/eye.2013.158
