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Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [1]; ; ; ; ;  [2];  [2]
  1. Shanghai Clinical Center for Diabetes Shanghai Diabetes Institute, Department of Endocrinology and Metabolism of Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai (China)
  2. Department of Ophthalmology, Shanghai Jiao Tong University Affiliated First People's Hospital, Haining Road 100, Shanghai 200080 (China)
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.
OSTI ID:
21143657
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 369; ISSN BBRCA9; ISSN 0006-291X
Country of Publication:
United States
Language:
English

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