摘要
CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angio- genic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout （CD146 EC-Ko） mice using the Tg（Tek-cre） system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146Ec-KO mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells （ECs）of CD146Ec-Ko mice. Mechanistic studies further confirmed that VEGF- induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/ NF-KB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146Ec-Ko mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angio- genic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout （CD146 EC-Ko） mice using the Tg（Tek-cre） system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146Ec-KO mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells （ECs）of CD146Ec-Ko mice. Mechanistic studies further confirmed that VEGF- induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/ NF-KB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146Ec-Ko mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
