Angiopoietin-2/Tie2 signaling involved in TNF-a induced peritoneal angiogenesis

PURPOSE: 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.