التفاصيل البيبلوغرافية
العنوان:
Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression
المؤلفون:
Emilia A. Korhonen , Aino Murtomäki , Sawan Kumar Jha , Andrey Anisimov , Anne Pink , Yan Zhang , Simon Stritt , Inam Liaqat , Lukas Stanczuk , Laura Alderfer , Zhiliang Sun , Emmi Kapiainen , Abhishek Singh , Ibrahim Sultan , Anni Lantta , Veli-Matti Leppänen , Lauri Eklund , Yulong He , Hellmut G. Augustin , Kari Vaahtomeri , Pipsa Saharinen , Taija Mäkinen , Kari Alitalo
المساهمون:
CAN-PRO - Translational Cancer Medicine Program, Research Programs Unit, University of Helsinki, Medicum, Michael Jeltsch / Principal Investigator, Cell Communication, Biosciences, Kari Alitalo / Principal Investigator, Molecular and Integrative Biosciences Research Programme, Department of Biochemistry and Developmental Biology, Helsinki In Vivo Animal Imaging Platform (HAIP), HUSLAB, Digital Precision Cancer Medicine (iCAN)
المصدر:
The Journal of Clinical Investigation
مصطلحات موضوعية:
ANGIOPOIETIN 2 , Cell- och molekylärbiologi , Vascular Endothelial Growth Factor C , LYMPHATIC VESSEL DEVELOPMENT , ANGIOGENESIS , VALVE , Receptors, TIE , Mice , Phosphatidylinositol 3-Kinases , VASCULATURE , Animals , Humans , Lymphedema , Lymphangiogenesis , GROWTH-FACTOR-C , GENE-EXPRESSION , Cancer och onkologi , RECEPTOR , Endothelial Cells , Ribonuclease, Pancreatic , General Medicine , Vascular Endothelial Growth Factor Receptor-3 , Receptor, TIE-2 , TIE1 , Cancer and Oncology , 1182 Biochemistry, cell and molecular biology , 3111 Biomedicine , Phosphatidylinositol 3-Kinase , Cell and Molecular Biology
الوصف:
Publisher Copyright: © 2022 American Society for Clinical Investigation. All rights reserved. Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C-induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with smallmolecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C-induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.
وصف الملف:
application/pdf
اللغة:
English
تدمد:
1558-8238
DOI:
10.1172/jci155478
الوصول الحر:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ea8df2eb80125ef12c0a24159c099fbTest
حقوق:
OPEN
رقم الانضمام:
edsair.doi.dedup.....7ea8df2eb80125ef12c0a24159c099fb
قاعدة البيانات:
OpenAIRE
