Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier
Zhongxiao Wang, Chi‐Hsiu Liu, Shuo Huang, Zhongjie Fu, Yohei Tomita, William Britton, Steve S. Cho, Chuck T. Chen, Ye Sun, Jian‐xing Ma, Xi He, Jing Chen
Abstract
) exhibit increased retinal vascular leakage and enhanced endothelial transcytosis. Wnt signaling directly controls the transcription of an endothelium-specific transcytosis inhibitor, major facilitator superfamily domain-containing protein 2a (MFSD2A), in a β-catenin-dependent manner. MFSD2A overexpression reverses Wnt deficiency-induced transcytosis in endothelial cells and in retinas. Moreover, Wnt signaling mediates MFSD2A-dependent vascular endothelium transcytosis through a caveolin-1 (CAV-1)-positive caveolae pathway. In addition, levels of omega-3 fatty acids are also decreased in Wnt signaling-deficient retinas, reflecting the basic function of MFSD2A as a lipid transporter. Our findings uncovered the Wnt/β-catenin/MFSD2A/CAV-1 axis as a key pathway governing endothelium transcytosis and inner BRB integrity.