You are here

PLoS One DOI:10.1371/journal.pone.0213831

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

Publication TypeJournal Article
Year of Publication2019
AuthorsStump, B, Shrestha, S, Lamattina, AM, Louis, PH, Cho, W, Perrella, MA, Ai, X, Rosas, IO, Wagner, FF, Priolo, C, Astin, J, El-Chemaly, S
JournalPLoS One
Volume14
Issue4
Pagese0213831
Date Published2019
ISSN1932-6203
Keywordsbeta Catenin, Cell Culture Techniques, Cell Line, Endothelial Cells, Glycogen Synthase Kinase 3 beta, Humans, Indoles, Lung, Lymphangiogenesis, Lymphatic Vessels, Maleimides, Microvessels, Phosphorylation, Protein Stability, RNA, Small Interfering, Signal Transduction, TOR Serine-Threonine Kinases
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.

DOI10.1371/journal.pone.0213831
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/30964887?dopt=Abstract

Alternate JournalPLoS ONE
PubMed ID30964887
PubMed Central IDPMC6456176
Grant ListR01 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