Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways.

PLoS One
Publication type
Journal Article
Authors
Keywords
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.

Year of Publication
2019
Journal
PLoS One
Volume
14
Issue
4
Pages
e0213831
Date Published
2019
ISSN
1932-6203
DOI
10.1371/journal.pone.0213831
PubMed ID
30964887
PubMed Central ID
PMC6456176
Links
Grant list
R01 HL130275 / HL / NHLBI NIH HHS / United States
R01 HL132991 / HL / NHLBI NIH HHS / United States
F32 HL140859 / HL / NHLBI NIH HHS / United States
T32 HL007633 / HL / NHLBI NIH HHS / United States