SOX7 suppresses endothelial-to-mesenchymal transitions by enhancing VE-cadherin expression during outflow tract development

Abstract The endothelial-to-mesenchymal transition (EndMT) is a critical process that occurs during the development of outflow tract (OFT). Malformations OFT can lead to occurrence conotruncal defect (CTD). SOX7 duplication has been reported in patients with congenital CTD, but its specific role remains poorly understood. To decipher this, histological analysis showed SRY-related HMG-box 7 (SOX7) was regionally expressed endocardial endothelial cells and mesenchymal OFT, where EndMT occurs. Experiments, using vitro collagen gel culture system, revealed negative regulator inhibited cell (EC) migration resulted decreased number cells. Forced expression blocked further improved adhesion protein vascular (VE)-cadherin (VE-cadherin). Moreover, VE-cadherin knockdown could partly reverse SOX7-mediated repression migration. Luciferase electrophoretic mobility shift assay (EMSA) demonstrated up-regulated by directly binding gene’s promoter coding exons splicing regions gene were also scanned 536 sporadic CTD 300 unaffected controls, which four heterozygous mutations. assays two variants weakened transactivation promoter. In conclusion, up-regulating endothelial-specific molecule VE-cadherin. mutations impaired regulating VE-cadherin, may give rise molecular mechanisms associated pathogenesis.