Search: WFRF:(Eklund Lauri) >
Lymphangiogenesis r...
Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression
-
- Korhonen, Emilia A. (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.;Heidelberg Univ, Med Fac Mannheim, European Ctr Angiosci ECAS, Mannheim, Germany.;Univ Bonn, Univ Hosp Bonn, Inst Neurovasc Cell Biol, Bonn, Germany.
-
- Murtomäki, Aino (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Jha, Sawan Kumar (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.;Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
-
show more...
-
- Anisimov, Andrey (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Pink, Anne (author)
- Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Zhang, Yan (author)
- Uppsala universitet,Vaskulärbiologi
-
- Stritt, Simon (author)
- Uppsala universitet,Vaskulärbiologi
-
- Liaqat, Inam (author)
- Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Stanczuk, Lukas (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
-
- Alderfer, Laura (author)
- Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.;Univ Notre Dame, Bioengn Grad Program, South Bend, IN USA.
-
- Sun, Zhiliang (author)
- Soochow Univ, Cam Su Genomk Resources Ctr, Collaborat Innovat Ctr Hematol, Cyrus Tang Hematol Ctr,State Key Lab Radiat Med &, Suzhou, Peoples R China.
-
- Kapiainen, Emmi (author)
- Univ Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu, Finland.
-
- Singh, Abhishek (author)
- Univ Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu, Finland.
-
- Sultan, Ibrahim (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Lantta, Anni (author)
- Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Leppänen, Veli-Matti (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Eklund, Lauri (author)
- Univ Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu, Finland.
-
- He, Yulong (author)
- Soochow Univ, Cam Su Genomk Resources Ctr, Collaborat Innovat Ctr Hematol, Cyrus Tang Hematol Ctr,State Key Lab Radiat Med &, Suzhou, Peoples R China.
-
- Augustin, Hellmut G. (author)
- German Canc Res Ctr DKFZ ZMBH Alliance, Div Vasc Oncol & Metastasis, Heidelberg, Germany.;Heidelberg Univ, Med Fac Mannheim, European Ctr Angiosci ECAS, Mannheim, Germany.
-
- Vaahtomeri, Kari (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Saharinen, Pipsa (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.
-
- Mäkinen, Taija (author)
- Uppsala universitet,Vaskulärbiologi
-
- Alitalo, Kari (author)
- Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.;Univ Helsinki, Fac Med, iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.
-
show less...
-
Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland.;Heidelberg Univ, Med Fac Mannheim, European Ctr Angiosci ECAS, Mannheim, Germany.;Univ Bonn, Univ Hosp Bonn, Inst Neurovasc Cell Biol, Bonn, Germany. Biomed Helsinki, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Helsinki, Finland. (creator_code:org_t)
- American Society for Clinical Investigation, 2022
- 2022
- English.
-
In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 132:15
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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 p110?? subunit or with small -molecule 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Korhonen, Emilia ...
-
Murtomäki, Aino
-
Jha, Sawan Kumar
-
Anisimov, Andrey
-
Pink, Anne
-
Zhang, Yan
-
show more...
-
Stritt, Simon
-
Liaqat, Inam
-
Stanczuk, Lukas
-
Alderfer, Laura
-
Sun, Zhiliang
-
Kapiainen, Emmi
-
Singh, Abhishek
-
Sultan, Ibrahim
-
Lantta, Anni
-
Leppänen, Veli-M ...
-
Eklund, Lauri
-
He, Yulong
-
Augustin, Hellmu ...
-
Vaahtomeri, Kari
-
Saharinen, Pipsa
-
Mäkinen, Taija
-
Alitalo, Kari
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Cell and Molecul ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Journal of Clini ...
- By the university
-
Uppsala University