作者
Daniela I Staquicini, Marina Cardó-Vila, Jimmy A Rotolo, Fernanda I Staquicini, Fenny HF Tang, Tracey L Smith, Aditya Ganju, Carmine Schiavone, Prashant Dogra, Zhihui Wang, Vittorio Cristini, Ricardo J Giordano, Michael G Ozawa, Wouter HP Driessen, Bettina Proneth, Glauco R Souza, Lina M Brinker, Achraf Noureddine, Ashley J Snider, Daniel Canals, Juri G Gelovani, Irina Petrache, Rubin M Tuder, Lina M Obeid, Yusuf A Hannun, Richard N Kolesnick, C Jeffrey Brinker, Renata Pasqualini, Wadih Arap
发表日期
2023/8/22
期刊
Proceedings of the National Academy of Sciences
卷号
120
期号
34
页码范围
e2220269120
出版商
National Academy of Sciences
简介
The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins. Here, we show that an endothelial lung-homing peptide (CGSPGWVRC) interacts with C16-ceramide, a bioactive sphingolipid that mediates several biological functions. Upon binding to cell surfaces, CGSPGWVRC triggers ceramide-rich platform formation, activates acid sphingomyelinase and ceramide production, without the associated downstream apoptotic signaling. We also show that the lung selectivity of CGSPGWVRC homing peptide is dependent on ceramide production in vivo. Finally, we demonstrate two potential applications for this lipid vascular targeting system: i) as a bioinorganic hydrogel for pulmonary imaging and ii) as a ligand-directed lung …
引用总数
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