Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis.
OBJECTIVE
Angiopoietin-2/Tie2 signaling has been found to play an important role in producing a vasculature in a variety of conditions. However, whether angiopoietin-2/Tie2 signaling is involved in peritoneal angiogenesis induced by TNF-α is not clear. In this study, we investigated the role of TNF-α on the function of human omental tissue microvascular endothelial cells (HOTMECs) and whether angiogenesis is inhibited by blocking angiopoietin-2/Tie2 signaling.


METHODS
Primary cultured HOTMECs were exposed to complete medium as control, medium containing 10 ng/ml TNF-α, a mixture of 10 ng/ml TNF-α plus 2 µg/ml sTie2/Fc or 2 µg/ml sTie2/Fc alone, respectively, as experimental groups. The proliferation of HOTMECs was measured by MTT assay. Expression of vascular endothelial growth factor (VEGF), Angiopoietin-2, and Tie2 were assessed by real-time PCR. We also investigated the angiogenesis of the HOTMECs by tube formation assay, their migration as well as their permeability to FITC-labeled BSA.


RESULTS
Compared to the cells in control, exposure to TNF-α or sTie2/Fc had no effect on proliferation of HOTMECs. TNF-α up-regulated the gene expression of VEGF, Angiopoietin-2, and Tie2 (p<0.05). TNF-α significantly promoted tube formation, migration and enhanced permeability of HOTMECs (p<0.05). Supplement with sTie2/Fc partially inhibited tube formation and migration (p<0.05). However, sTie2/Fc did not inhibit the increased permeability induced by TNF-α (p>0.05).


CONCLUSIONS
Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis may provide an alternative way to prevent peritoneal angiogenesis.
Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China.
Jiangzi
J
Yuan
Wei
W
Fang
Aiwu
A
Lin
Zhaohui
Z
Ni
Jiaqi
J
Qian
D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010539:Permeability; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042702:Angiopoietin-2; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2