Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs.
Poly(ADP-ribose)polymerase (PARP) inhibitors decrease angiogenesis through reducing vascular endothelium growth factor (VEGF) induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In contrast to VEGF, pigment epithelium-derived factor (PEDF) has been demonstrated to act as a strong endogenous inhibitor of angiogenesis. Here, we show that PARP inhibition with a specific inhibitor PJ-34 or specific PARP antisense oligonucleotide upregulates hyperglycemia-induced PEDF expression in HUVECs in a dose-dependent manner. This results in the retard of activation of p38 MAP kinase and the concomitant decrease in cell apoptosis. These results give the first direct demonstration that PEDF might represent a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent.
Chen
Haibing
H
Shanghai Clinical Center for Diabetes Shanghai Diabetes Institute, Department of Endocrinology and Metabolism of Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Jia
Weiping
W
Xu
Xun
X
Fan
Ying
Y
Zhu
Dongqing
D
Wu
Haixiang
H
Xie
Zhenggao
Z
Zheng
Zhi
Z
D017209:Apoptosis; D002478:Cells, Cultured; D024161:Collagen Type XI / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D005136:Eye Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D024161:Collagen Type XI; D005136:Eye Proteins; D005947:Glucose; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C499319:COL11A2 protein, human