ERK1/2 Signaling Pathways Involved in VEGF Release in Diabetic Rat Retina

Abstract

 

Purpose:

 

VEGF is one of the major factors to promote diabetic retinopathy(DR). A better understanding of the signaling pathway in VEGFregulation is of clinical importance to identify more precisetherapeutic targets for diabetic retinopathy. The ERK1/2 pathwayhas been verified to play a key role in some oncoma and hematologicdisease to mediate VEGF release. This research aims to determinewhether the ERK1/2 pathway also play a major role in VEGF releasein diabetic retinopathy development.

 

Methods:

 

SD rats were induced to diabetes by STZ injection and monitoredat several time points (1 week, 2 weeks, 3 weeks, 4 weeks, 8weeks, 12 weeks) for ERK1/2 phosphorylation, AP-1 activity andconcentration,and VEGF protein and mRNA expression using immunohistochemicaland biochemical methods. And in order to verivied ERK1/2 andthe downstream transcription factor AP-1 take part in the mechanismsof VEGF release in diabetes retina, U0126, an ERK1/2 specificinhibitor, was injected into the vitreous cavity in rats beforethey were induced to diabetes. And the phosphorylation of ERK1/2,activation of AP-1, and VEGF were researched by same ways.

 

Results:

 

The ERK1/2 pathway rapidly activated 1 week after inducing diabetes(Fig1). AP-1, the downstream transcription factor of ERK1/2,also activated, and VEGF became highly regulated in a similartrend. U0126 down regulated the expression of VEGF, in additionto ERK1/2 and AP-1 activity (Fig2).

 

Conclusions:

 

ERK1/2 signalling pathyway is involved in VEGF release in diabeticrat retina; therefore, ERK1/2 may be a potential therapeutictarget of the DR.  

 

 

Keywords: vascular endothelial growth factor • diabetic retinopathy • signal transduction