Induction of VE-cadherin in rat placental trophoblasts by VEGF through a NO-dependent pathway.
Vascular endothelial-cadherin (VE-cadherin), a calcium-dependent homotypic adhesion molecule, contributes to endothelial assembly and VEGF-mediated survival during angiogenesis. In human term placentas, villous vessels and extravillous cytotrophoblasts express VE-cadherin. Therefore, the purpose of this study was to examine if VEGF modulated placental development by increasing the expression of VE-cadherin in rat placentas. Placental tissues from rats on gestation days 14 (G14), 18 (G18) and 21 (G21) were used. Western blot analysis and immunohistochemistry were performed to detect the protein abundance and the distribution of VE-cadherin. A nitric oxide analyzer was used to measure the released nitric oxide (NO) from placental explant culture. With the progression of pregnancy, the abundance of VE-cadherin and the intensity of the immunoreactive staining for VE-cadherin in endovascular trophoblasts and labyrinth trophoblasts were decreased. In explant culture, VEGF (0.01-1.0 ng/ml) increased the protein abundance of VE-cadherin. SNP (an NO donor) or L-arginine (substrate for eNOS) induced the expression of VE-cadherin with the increase of NO production. L-NAME (a NOS inhibitor) reduced the VEGF-increased expression and L-arginine reversed the inhibitory effect of L-NAME. In conclusion, VEGF plays an important role in placental development by the induction of VE-cadherin in trophoblasts, which, in part, maintains the survival of labyrinth trophoblast in rat placentas.
Chang
Chih-Ching
CC
Graduate Institute of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chang
Torng-Yuo
TY
Yu
Chen-Hsiang
CH
Tsai
Mei-Ling
ML
D000818:Animals; D015703:Antigens, CD; D001120:Arginine / Q000494:pharmacology; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D000099152:Cadherin 5
D015703:Antigens, CD; D001120:Arginine; D015820:Cadherins; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D009599:Nitroprusside; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5