ERK1/2 signaling pathways involved in VEGF release in diabetic rat retina.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is one of the major factors promoting diabetic retinopathy (DR). A better understanding of the signaling pathway in VEGF regulation is of clinical importance to identify more precise therapeutic targets for diabetic retinopathy. The ERK1/2 signaling pathway has been shown to play a key role in some oncoma and hematologic diseases by mediating VEGF release. This research was conducted to determine whether the ERK1/2 signaling pathway also plays a major role in VEGF release in DR development.


METHODS
One hundred Sprague-Dawley (SD) rats were induced to diabetes by streptozotocin (STZ) injection and monitored at several time points (1, 2, 3, 4, 8, and 12 weeks) for ERK1/2 phosphorylation, Activator protein (AP)-1 activity and concentration, and VEGF protein and mRNA expression, using immunohistochemical and biochemical methods. RESULTS. The ERK1/2 signaling pathway was rapidly activated 1 week after diabetes was induced. AP-1, the downstream transcription factor of ERK1/2, was also activated, and VEGF became highly regulated in a similar trend. U0126, an inhibitor of ERK1/2, also downregulated VEGF expression, in addition to ERK1/2 and AP-1 activity.


CONCLUSIONS
ERK1/2 signaling pathway is involved in VEGF release in diabetic rat retina; therefore, ERK1/2 may be a potential therapeutic target of DR.
Ye
Xiaofeng
X
EENT Hospital, Eye Institute, Fudan University, Shanghai, China.
Xu
Gezhi
G
Chang
Qing
Q
Fan
Jiaweng
J
Sun
Zhongcui
Z
Qin
Yaowu
Y
Jiang
Alice C
AC
D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014822:Vitreous Body / Q000187:drug effects
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C113580:U 0126; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3