Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways.
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...
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Online Access: | https://doi.org/10.1371/journal.pone.0213831 |
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doaj-5bd9212dd63c4546b6cdf5e5cfdc3da12021-03-03T21:09:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021383110.1371/journal.pone.0213831Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways.Benjamin StumpShikshya ShresthaAnthony M LamattinaPierce H LouisWoohyun ChoMark A PerrellaXingbin AiIvan O RosasFlorence F WagnerCarmen PrioloJonathan AstinSouheil El-ChemalyLymphatic 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.https://doi.org/10.1371/journal.pone.0213831 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Benjamin Stump Shikshya Shrestha Anthony M Lamattina Pierce H Louis Woohyun Cho Mark A Perrella Xingbin Ai Ivan O Rosas Florence F Wagner Carmen Priolo Jonathan Astin Souheil El-Chemaly |
spellingShingle |
Benjamin Stump Shikshya Shrestha Anthony M Lamattina Pierce H Louis Woohyun Cho Mark A Perrella Xingbin Ai Ivan O Rosas Florence F Wagner Carmen Priolo Jonathan Astin Souheil El-Chemaly Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways. PLoS ONE |
author_facet |
Benjamin Stump Shikshya Shrestha Anthony M Lamattina Pierce H Louis Woohyun Cho Mark A Perrella Xingbin Ai Ivan O Rosas Florence F Wagner Carmen Priolo Jonathan Astin Souheil El-Chemaly |
author_sort |
Benjamin Stump |
title |
Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways. |
title_short |
Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways. |
title_full |
Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways. |
title_fullStr |
Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways. |
title_full_unstemmed |
Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways. |
title_sort |
glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mtor-independent pathways. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0213831 |
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