Vascular endothelial growth factor gene expression in a retinal pigmented cell is up-regulated by glucose deprivation through 3' UTR.
Diabetic retinopathy is known to be worsened when hypoglycemia occurs, however the pathogenic mechanisms are not defined. Vascular endothelial growth factor (VEGF) is increased in ocular fluid with diabetic retinopathy and linked with development of retinopathy. In this study, we examined whether glucose deficiency could up-regulate VEGF levels in retinal pigmented cells. Exposure to glucose deprived medium induced 30% up-regulation of VEGF mRNA. In hypoxia, as one of the most well-known inducer of VEGF, its up-regulation mechanism is mainly due to increase of transcription of VEGF gene via hypoxia response element in 5'-untranslated region (5'-UTR). We examined the role of 5'-UTR and 3'-UTR of VEGF gene in glucose deprived conditions using luciferase assay system. 5'-UTR containing reporter vector did not show increase of activity in glucose deprived conditions in contrast to the result in oxygen deprived condition. Both 5'-UTR and 3'-UTR containing vector demonstrated significant increase of activity in glucose deficient conditions compared with 5'-UTR containing vector. These findings suggest 3'-UTR of VEGF gene is important for increasing mRNA level in glucose deprived condition.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8575, Japan.
Kaoruko
K
Iida
Yasushi
Y
Kawakami
Hirohito
H
Sone
Hiroaki
H
Suzuki
Sigeru
S
Yatoh
Kazumasa
K
Isobe
Kazuhiro
K
Takekoshi
Nobuhiro
N
Yamada
D020413:3' Untranslated Regions / Q000235:genetics*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D005947:Glucose / Q000172:deficiency*; D008156:Luciferases / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D010100:Oxygen / Q000502:physiology; D010858:Pigmentation / Q000502:physiology; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020413:3' Untranslated Regions; D000199:Actins; D003470:Culture Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D008156:Luciferases; D005947:Glucose; D010100:Oxygen