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Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways
- Source :
- PLoS ONE, Vol 14, Iss 4, p e0213831 (2019)
- Publication Year :
- 2018
-
Abstract
- Lymphatic vessels play an important role in health and in disease. In this study, we evaluated the effects of GSK3-β inhibition on lung lymphatic endothelial cells in vitro. Pharmacological inhibition and silencing of GSK3-β resulted in increased lymphangiogenesis of lung lymphatic endothelial cells. To investigate mechanisms of GSK3-β-mediated lymphangiogenesis, we interrogated the mammalian/mechanistic target of rapamycin pathway and found that inhibition of GSK3-β resulted in PTEN activation and subsequent decreased activation of AKT, leading to decreased p-P70S6kinase levels, indicating inhibition of the mTOR pathway. In addition, consistent with a negative role of GSK3-β in β-catenin stability through protein phosphorylation, we found that GSK3-β inhibition resulted in an increase in β-catenin levels. Simultaneous silencing of β-catenin and inhibition of GSK3-β demonstrated that β-catenin is required for GSK3-β-induced lymphangiogenesis.
- Subjects :
- 0301 basic medicine
animal structures
Indoles
government.form_of_government
Science
Cell Culture Techniques
macromolecular substances
Cell Line
Maleimides
03 medical and health sciences
0302 clinical medicine
GSK-3
Humans
Lymphangiogenesis
Phosphorylation
RNA, Small Interfering
Mechanistic target of rapamycin
Protein kinase B
Lung
PI3K/AKT/mTOR pathway
beta Catenin
Lymphatic Vessels
Multidisciplinary
Glycogen Synthase Kinase 3 beta
biology
Chemistry
Protein Stability
TOR Serine-Threonine Kinases
Endothelial Cells
Cell biology
Lymphatic Endothelium
030104 developmental biology
030220 oncology & carcinogenesis
Catenin
Microvessels
biology.protein
government
Medicine
Signal Transduction
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 14
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....69881651e6b6a4e7195c0f73b6a7def7