PT  - JOURNAL ARTICLE
AU  - Wang, Zhongxiao
AU  - Liu, Chi-Hsiu
AU  - Huang, Shuo
AU  - Fu, Zhongjie
AU  - Tomita, Yohei
AU  - Britton, William R.
AU  - Cho, Steve S.
AU  - Chen, Chuck T.
AU  - Sun, Ye
AU  - Ma, Jian-xing
AU  - He, Xi
AU  - Chen, Jing
TI  - Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier
AID  - 10.1126/sciadv.aba7457
DP  - 2020 Aug 01
TA  - Science Advances
PG  - eaba7457
VI  - 6
IP  - 35
4099  - http://advances.sciencemag.org/content/6/35/eaba7457.short
4100  - http://advances.sciencemag.org/content/6/35/eaba7457.full
SO  - Sci Adv2020 Aug 01; 6
AB  - Breakdown of the blood-retinal barrier (BRB) causes retinal edema and vision loss. We investigated the role of Wnt signaling in maintaining the BRB by limiting transcytosis. Mice lacking either the Wnt co-receptor low-density lipoprotein receptor–related protein 5 (Lrp5−/−) or the Wnt ligand Norrin (Ndpy/−) 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.