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DOI | 10.1002/2016GL071921 |
The role of fatty acid beta-oxidation in lymphangiogenesis | |
Wong, Brian W.1,2; Wang, Xingwu1,2; Zecchin, Annalisa1,2; Thienpont, Bernard3,4; Cornelissen, Ivo1,2; Kalucka, Joanna1,2; Garcia-Caballero, Melissa5; Missiaen, Rindert1,2; Huang, Hongling1,2; Burning, Ulrike1,2; Blacher, Silvia; Vinckier, Stefan1,2; Goveia, Jermaine1,2; Knobloch, Marlen; Zhao, Hui3,4; Dierkes, Cathrin7; Shi, Chenyan1,2; Haegerling, Rene7; Moral-Darde, Veronica1,2,8; Wyns, Sabine1,2; Lippens, Martin1,2; Jessberger, Sebastian6; Fendt, Sarah-Maria9,10,11; Luttun, Aernout12; Noel, Agnes; Kiefer, Friedemann7; Ghesquiere, Bart; Moons, Lieve1,13; Schoonjans, Luc1,2; Dewerchin, Mieke1,2; Eelen, Guy1,2; Lambrechts, Diether3,4; Carmeliet, Peter1,2 | |
2017-02-02 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 542期号:7639页码:49-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Belgium; Switzerland; Germany |
英文摘要 | Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid beta-oxidation, impairs lymphatic development. LECs use fatty acid beta-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid beta-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1-target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Notably, blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl coenzyme A by supplementing acetate rescues this process in vivo. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000396119300030 |
WOS关键词 | ENDOTHELIAL-CELLS ; LYMPHATIC VASCULATURE ; HISTONE H3 ; IDENTITY ; PROX1 ; TUMOR ; GENE ; MAINTENANCE ; INHIBITION ; METABOLISM |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/27563 |
专题 | 气候变化 |
作者单位 | 1.Katholieke Univ Leuven, Dept Oncol, Lab Angiogenesis & Vasc Metab, B-3000 Leuven, Belgium; 2.VIB, VIB Vesalius Res Ctr, Lab Angiogenesis & Vasc Metab, B-3000 Leuven, Belgium; 3.Katholieke Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium; 4.VIB, VIB Vesalius Res Ctr, Lab Translat Genet, B-3000 Leuven, Belgium; 5.Univ Liege, GIGA Canc, Lab Biol Tumor & Dev, B-4000 Liege, Belgium; 6.Univ Zurich, Brain Res Inst, Fac Med & Sci, CH-8057 Zurich, Switzerland; 7.Max Planck Inst Mol Biomed, Dept Vasc Cell Biol, Mammalian Cell Signaling Lab, D-48161 Munster, Germany; 8.VIB, VIB Vesalius Res Ctr, Metabol Core Facil, B-3000 Leuven, Belgium; 9.VIB, VIB Vesalius Res Ctr, Lab Cellular Metab & Metab Regulat, B-3000 Leuven, Belgium; 10.Katholieke Univ Leuven, Dept Oncol, Lab Cellular Metab & Metab Regulat, B-3000 Leuven, Belgium; 11.Leuven Canc Inst LKI, B-3000 Leuven, Belgium; 12.Katholieke Univ Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, B-3000 Leuven, Belgium; 13.Katholieke Univ Leuven, Dept Biol, Anim Physiol & Neurobiol Sect, Lab Neural Circuit Dev & Regenerat, B-3000 Leuven, Belgium |
推荐引用方式 GB/T 7714 | Wong, Brian W.,Wang, Xingwu,Zecchin, Annalisa,et al. The role of fatty acid beta-oxidation in lymphangiogenesis[J]. NATURE,2017,542(7639):49-+. |
APA | Wong, Brian W..,Wang, Xingwu.,Zecchin, Annalisa.,Thienpont, Bernard.,Cornelissen, Ivo.,...&Carmeliet, Peter.(2017).The role of fatty acid beta-oxidation in lymphangiogenesis.NATURE,542(7639),49-+. |
MLA | Wong, Brian W.,et al."The role of fatty acid beta-oxidation in lymphangiogenesis".NATURE 542.7639(2017):49-+. |
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