Details

Autor(en) / Beteiligte

• Wang, Zhongxiao
• Liu, Chi-Hsiu
• Huang, Shuo
• Fu, Zhongjie
• Tomita, Yohei
• Britton, William R
• Cho, Steve S
• Chen, Chuck T
• Sun, Ye
• Ma, Jian-Xing
• He, Xi
• Chen, Jing

Titel

Wnt signaling activates MFSD2A to suppress vascular endothelial transcytosis and maintain blood-retinal barrier

Ist Teil von

• Science advances, 2020-08, Vol.6 (35), p.eaba7457-eaba7457

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 ( ) or the Wnt ligand Norrin ( ) 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.