Article

Coordinated expression of Ets-1, pERK1/2, and VEGF in retina of streptozotocin-induced diabetic rats.

Department of Ophthalmology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Ophthalmic Research (impact factor: 1.56). 02/2007; 39(4):224-31. DOI:10.1159/000104831 pp.224-31
Source: PubMed

ABSTRACT To investigate the role played by E26 transformation-specific-1 (Ets-1), a transcription factor, and extracellular signal-regulated kinase 1/2 (ERK1/2) in the expression of vascular endothelial growth factor (VEGF), and the interaction of Ets-1 and ERK1/2 in the retina of diabetic rats.
Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ). To follow the time course in the expression of Ets-1, phosphorylated ERK1/2 (pERK1/2), and VEGF, rats were killed at 1, 2, 4, and 8 weeks after the injection of STZ, and total proteins were extracted from the isolated retinas. An adenovirus vector encoding dominant-negative Ets-1 and an inhibitor of PD98059 was injected intravitreally to investigate the effects of Ets-1 blockade and ERK1/2 inhibition on the expression of VEGF. Four weeks after the first intravitreal injection, total proteins and total RNA were extracted from the retinas for Western blot and Northern blot analyses.
The expression of Ets-1, pERK1/2, and VEGF in the retina increased in a time-dependent manner after STZ injection. The phosphorylation of ERK1/2 and protein level of VEGF were significantly reduced following intravitreal Ets-1. Inhibition of ERK1/2 phosphorylation resulted in a significant reduction in the expression of Ets-1 and the level of VEGF protein.
These results indicate that in the retina of STZ-induced diabetic rats: (1) the alterations of Ets-1, pERK1/2, and VEGF are approximately synchronized; (2) the phosphorylation of ERK1/2 is regulated by the expression of Ets-1; (3) the production of Ets-1 protein is dependent on the ERK1/2 pathway, and (4) the protein level of VEGF is regulated by both Ets-1 expression and ERK1/2 phosphorylation. We propose that VEGF, Ets-1, and ERK1 act synergistically in the development of diabetic retinopathy.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

8 weeks
 
adenovirus vector encoding dominant-negative Ets-1
 
ERK1 act synergistically
 
ERK1/2 inhibition
 
ERK1/2 phosphorylation
 
Ets-1 protein
 
extracellular signal-regulated kinase 1/2
 
first intravitreal injection
 
intraperitoneal injection
 
intravitreal Ets-1
 
isolated retinas
 
Northern blot analyses
 
phosphorylated ERK1/2
 
STZ injection
 
STZ-induced diabetic rats
 
time course
 
time-dependent manner
 
transcription factor
 
vascular endothelial growth factor
 
VEGF protein