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| 1 | Meningeal lymphatic vessels regulate brain tumor drainage and immunity显示文摘Recent studies have shown that meningeal lymphatic vessels(MLVs),which are located both dorsally and basally beneath the skull,provide a route for draining macromolecules and trafficking immune cells from the central nervous system(CNS)into cervical lymph nodes(CLNs),and thus represent a potential therapeutic target for treating neurodegenerative and neuroinflammatory diseases.However,the roles of MLVs in brain tumor drainage and immunity remain unexplored.Here we show that dorsal MLVs undergo extensive remodeling in mice with intracranial gliomas or metastatic melanomas.RNA-seq analysis of MLV endothelial cells revealed changes in the gene sets involved in lymphatic remodeling,fluid drainage,as well as inflammatory and immunological responses.Disruption of dorsal MLVs alone impaired intratumor fluid drainage and the dissemination of brain tumor cells to deep CLNs(dCLNs).Notably,the dendritic cell(DC)trafficking from intracranial tumor tissues to dCLNs decreased in mice with defective dorsal MLVs,and increased in mice with enhanced dorsal meningeal lymphangiogenesis.Strikingly,disruption of dorsal MLVs alone,without affecting basal MLVs or nasal LVs,significantly reduced the efficacy of combined anti-PD-1/CTLA-4 checkpoint therapy in striatal tumor models.Furthermore,mice bearing tumors overexpressing VEGF-C displayed a better response to anti-PD-1/CTLA-4 combination therapy,and this was abolished by CCL21/CCR7 blockade,suggesting that VEGF-C potentiates checkpoint therapy via the CCL21/CCR7 pathway.Together,the results of our study not only demonstrate the functional aspects of MLVs as classic lymphatic vasculature,but also highlight that they are essential in generating an efficient immune response against brain tumors. | Xueting Hu Qiuping Deng Lu Ma Qingqing Li Yidong Chen Yuhan Liao Fan Zhou Chen Zhang Linlin Shao Jun Feng Tubao He Weihai Ning Yan Kong Yingqing Huo Aibin He Bing Liu Jingjing Zhang Ralf Adams Yulong He Fuchou Tang Xiuwu Bian Jincai Luo | 2020 | Cell Research2020，30，3： | 11 |
| 2 | Hypertensive stretch regulates endothelial exocytosis of WeibeI-Palade bodies through VEGF receptor 2 signaling pathways显示文摘Weibel-Palade 身体(WPB ) 的调整 endothelial exocytosis,在白血球 trafficking 的第一个阶段,在发炎和损害起一个枢轴的作用。尖锐的机械段仔细与脉管的发炎被联系了,尽管精确机制是未知的。这里,我们证明那高血压的段通过 VEGF 受体 2 调整 endothelial 房间(EC ) 的 WPB 的 exocytosis (VEGFR2 ) 表明小径。段触发一个快速的版本(在分钟以内) 从在有教养的人的 EC 的 WPB 的 von Willebrand 因素和 interleukin-8,通过 P-selectin 的 translocation 把在白血球和 EC 之间的相互作用提升到房间膜。我们进一步证明那高血压的段显著地导致未经触动的 EC 的 P-selectin translocation 并且两个都提高白血球粘附前 vivo 并且在 vivo。导致段的 endothelial exocytosis 经由 VEGFR2/PLCγ 被调停; 1/calcium 小径。有趣地,段也经由一条 VEGFR2/Akt/nitric 氧化物小径导致否定反馈。如此的双效果在颈动脉动脉片断,以及在尖锐高血压的老鼠模型用药理学和基因途径被证实。这些研究为 endothelial exocytosis 作为有势力收缩筋揭示机械段,它被 VEGFR2 发信号调制。因此, VEGFR2 发信号小径可以在限制高血压的段相关的发炎代表新奇治疗学的目标。 | Yan Xiong Zhenqian Hu Xiaofan Han Beibei Jiang Rongli Zhan Xiaoyu Zhang Yao Lu Chenyang Geng Wei Li Yulong He Yingqing Huo Masabuml Shlbuya Jincai Luo | 2013 | Cell Research2013，23，6： | 7 |
| 3 | Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity显示文摘As a first-line treatment,radiotherapy(RT)is known to modulate the immune microenvironment of glioma,but it is unknown whether the meningeal lymphatic vessel(MLV)-cervical lymph node(CLN)network regulates the process or influences RT efficacy.Here,we show that the MLV-CLN network contributes to RT efficacy in brain tumors and mediates the RT-modulated anti-tumor immunity that is enhanced by vascular endothelial growth factor C(VEGF-C).Meningeal lymphatic dysfunction impaired tumorderived dendritic cell(DC)trafficking and CD8^(+)T cell activation after RT,whereas tumors overexpressing VEGF-C with meningeal lymphatic expansion were highly sensitive to RT.Mechanistically,VEGF-C-driven modulation of RT-triggered anti-tumor immunity was attributed to C-C Motif Chemokine Ligand 21(CCL21)-dependent DC trafficking and CD8^(+)T cell activation.Notably,delivery of VEGF-C mRNA significantly enhanced RT efficacy and anti-tumor immunity in brain tumors.These findings suggest an essential role of the MLV-CLN network in RT-triggered anti-tumor immunity,and highlight the potential of VEGF-C mRNA for brain tumor therapy. | Changping Zhou Lu Ma Han Xu Yingqing Huo Jincai Luo | 2022 | Cell Research2022，32，6： | 3 |
| 4 | Endothelial mechanosensors: the gatekeepers of vascular homeostasis and adaptation under mechanical stress显示文摘Endothelial cells(ECs)not only serve as a barrier between blood and extravascular space to modulate the exchange of fluid,macromolecules and cells,but also play a critical role in regulation of vascular homeostasis and adaptation under mechanical stimulus via intrinsic mechanotransduction.Recently,with the dissection of microdomains responsible for cellular responsiveness to mechanical stimulus,a lot of mechanosensing molecules(mechanosensors)and pathways have been identified in ECs.In addition,there is growing evidence that endothelial mechanosensors not only serve as key vascular gatekeepers,but also contribute to the pathogenesis of various vascular disorders.This review focuses on recent findings in endothelial mechanosensors in subcellular microdomains and their roles in regulation of physiological and pathological functions under mechanical stress. | DENG QiuPing HUO YingQing LUO JinCai | 2014 | Science China(Life Sciences)2014，57，8： | 2 |
| 5 | Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation显示文摘 | Chunshui Pan Yingqing Huo Xiaojin An Gurbakhshish Singh Meng Chen Zhaoxiang Yang Junxue Pu Jian Li | 2011 | 2011 (3-4)2011，，3： | 1 |
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