该研究团队提出了一种体内血管腔表面的蛋白质组学分析方法，广泛适用于任何脊椎动物。定量质谱分析揭示了无主题脑血管管腔表面蛋白质组及其从发育到衰老的时间演变。体内遗传扰动发现，精氨酸转运体SLC7A1和一氧化氮合酶NOS3是新生小鼠血脑屏障完整性所必需的，而成年小鼠则不需要，而透明质酸降解酶HYAL2则在整个生命周期中保护屏障。通过表征血管腔表面的蛋白质组动力学，该研究将一氧化氮和透明质酸的代谢与血脑屏障完整性联系起来。
据悉，在血组织界面，脉管腔表面对分子转运、信号转导和细胞外渗至关重要。
附：英文原文
Title: Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators
Author: Zijian Zhu, Zuzhi Jiang, Yupu Wang, Khanh Nguyen, Yuxiang Zhang, Cameron Genxuan Lian, D. R. Mani, Jun Zheng, Lang Ding, Shihong Max Gao, Ruyue Alps Xia, Anne Kuszpit, Sarah Lindo, Crystall Lopez, Catherine Lindsey, Brooke Groff, Xinhong Chen, Jiahui Wu, Weiliang Xia, Wei Li, Xiaorong Liu, Viviana Gradinaru, Steven A. Carr, Namrata D. Udeshi, Jiefu Li
Issue&Volume: 2026-04-09
Abstract: At the blood-tissue interface, vasculature luminal surface is critical for molecular transport, signaling transduction, and cell extravasation. Here, we present a method for proteomic profiling of the vasculature luminal surface in vivo, broadly applicable to any vertebrate. Quantitative mass spectrometry revealed the luminal surface proteome of the mouse brain vasculature and its temporal evolution from development to aging. In vivo genetic perturbation found that the arginine transporter SLC7A1 and the nitric oxide synthase NOS3 are needed for blood-brain barrier integrity in neonatal but not adult mice, whereas the hyaluronan degradation enzyme HYAL2 safeguards the barrier throughout the lifespan. By characterizing the proteomic dynamics of the vasculature luminal surface, the study links the metabolism of nitric oxide and hyaluronan to blood-brain barrier integrity.
DOI: aea2100
Source: https://www.science.org/doi/10.1126/science.aea2100