| First Author | Cui XB | Year | 2013 |
| Journal | Cardiovasc Res | Volume | 99 |
| Issue | 4 | Pages | 632-9 |
| PubMed ID | 23695833 | Mgi Jnum | J:218659 |
| Mgi Id | MGI:5618091 | Doi | 10.1093/cvr/cvt121 |
| Citation | Cui XB, et al. (2013) Response gene to complement 32 deficiency causes impaired placental angiogenesis in mice. Cardiovasc Res 99(4):632-9 |
| abstractText | AIMS: The objectives of this study are to determine the role of response gene to complement 32 (RGC-32) in the placental angiogenesis during pregnancy and explore the underlying mechanisms. METHODS AND RESULTS: RGC-32-deficient (RGC32(-/-)) mice were generated from C57BL/6 embryonic stem cells with deletion of exon 2 and 3 of the RGC-32 gene. Most of the RGC32(-/-) mice can survive. However, their body sizes were much smaller compared with their wild-type littermates when they were born. By examining the embryo development and placentas at 16.5 days post-coitum, we found that RGC32(-/-) embryos and foetal placentas were significantly smaller than the wild-type. Further analysis showed that the labyrinth zone of RGC32(-/-) placenta was smaller with defective angiogenesis. Mechanistically, vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and placental growth factor (PlGF) were significantly down-regulated in RGC32(-/-) placentas, suggesting that VEGFR2 and PlGF may mediate RGC-32 function in placental angiogenesis. Indeed, knockdown of RGC-32 by shRNA inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation while blocking VEGFR2 expression. RGC-32 appeared to regulate VEGFR2 expression via activation of NF-kB. Moreover, RGC-32 regulated trophoblasts proliferation via control of PlGF expression. CONCLUSION: Absence of RGC-32 caused foetal growth restriction through interrupting the placental angiogenesis, which was due to the decrease in VEGFR2 expression through the NF-kB-dependent pathway in endothelial cells and PlGF expression in trophoblasts. |
