| First Author | Wang Z | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 35 | Pages | eaba7457 |
| PubMed ID | 32923627 | Mgi Jnum | J:328478 |
| Mgi Id | MGI:6790751 | Doi | 10.1126/sciadv.aba7457 |
| Citation | Wang Z, et al. (2020) Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier. Sci Adv 6(35):eaba7457 |
| abstractText | 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 (Ndp(y/-) ) 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 beta-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/beta-catenin/MFSD2A/CAV-1 axis as a key pathway governing endothelium transcytosis and inner BRB integrity. |
