Regulation of transforming growth factor-beta, basic fibroblast growth factor, and vascular endothelial cell growth factor mRNA in peripheral blood leukocytes in patients with diabetic retinopathy.
In the present study, we examined the effect of glucose concentration on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) mRNA using reverse transcriptase-polymerase chain reaction (RT-betaCR) in normal healthy leukocytes in vitro and in leukocytes from patients with type 1 diabetes mellitus. In vitro, the level of TGF-beta mRNA was altered in response to the glucose concentration (maximum at 10 mmol/L), while bFGF mRNA remained relatively constant and VEGF mRNA varied with no clear correlation with the glucose concentration. Leukocytes from type 1 patients showed no difference in bFGF or TGF-beta mRNA levels compared with age-matched healthy controls. However, VEGF mRNA was significantly lower in type 1 patients compared with controls (P < .05). When the patients were subtyped according to the severity of retinopathy, the level of TGF-beta mRNA was elevated selectively in patients with evidence of active new retinal vessels (P < .01) and VEGF121 mRNA was reduced in patients with mild to moderate retinopathy. Thus, leukocyte growth factor mRNAs respond to acute changes in the glucose concentration in vitro, and are differentially expressed in type 1 diabetic patients during the course of the disease.
Knott
R M
RM
Department of Ophthalmology, University of Aberdeen, Foresterhill, UK.
Pascal
M M
MM
Ferguson
C
C
Leiper
J
J
Olson
J
J
Muckersie
E
E
Robertson
M
M
Forrester
J V
JV
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood*; D004587:Electrophoresis, Agar Gel; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D005947:Glucose; D006442:Glycated Hemoglobin; D008222:Lymphokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C467484:VEGFA protein, human