Differential angiogenic properties of lithium chloride in vitro and in vivo
Standard
Differential angiogenic properties of lithium chloride in vitro and in vivo. / Zeilbeck, Ludwig F; Müller, Birgit; Knobloch, Verena; Tamm, Ernst R; Ohlmann, Andreas.
in: PLOS ONE, Jahrgang 9, Nr. 4, 2014, S. e95546.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Differential angiogenic properties of lithium chloride in vitro and in vivo
AU - Zeilbeck, Ludwig F
AU - Müller, Birgit
AU - Knobloch, Verena
AU - Tamm, Ernst R
AU - Ohlmann, Andreas
PY - 2014
Y1 - 2014
N2 - Wnt/β-catenin signaling induced by the Norrin/Frizzled-4 pathway has been shown to improve capillary repair following oxygen induced retinopathy (OIR) in the mouse, a model for retinopathy of prematurity. Here we investigated if treatment with the monovalent cation lithium that has been shown to augment Wnt/β-catenin signaling in vitro and in vivo has similar effects. In cultured human microvascular endothelial cells, LiCl as well as SB 216763, another small molecule that activates Wnt/β-catenin signaling, induced proliferation, survival and migration, which are all common parameters for angiogenic properties in vitro. Moreover, treatment with both agents caused an increase in the levels of β-catenin and their translocation to nuclei while quercetin, an inhibitor of Wnt/β-catenin signaling, completely blocked the effects of LiCl on proliferation. In mice with OIR, intraperitonal or intravitreal treatment with LiCl markedly increased the retinal levels of β-catenin, but did not improve capillary repair. In contrast, repair was significantly improved following intravitreal treatment with Norrin. The effects of LiCl on HDMEC in vitro have minor relevance for OIR in vivo, and the influence of the Norrin/Frizzled-4 pathway on capillary repair in OIR is not reproducible upon enhancing Wnt/β-catenin signaling by LiCl treatment strongly indicating the presence of additional and essential mechanisms.
AB - Wnt/β-catenin signaling induced by the Norrin/Frizzled-4 pathway has been shown to improve capillary repair following oxygen induced retinopathy (OIR) in the mouse, a model for retinopathy of prematurity. Here we investigated if treatment with the monovalent cation lithium that has been shown to augment Wnt/β-catenin signaling in vitro and in vivo has similar effects. In cultured human microvascular endothelial cells, LiCl as well as SB 216763, another small molecule that activates Wnt/β-catenin signaling, induced proliferation, survival and migration, which are all common parameters for angiogenic properties in vitro. Moreover, treatment with both agents caused an increase in the levels of β-catenin and their translocation to nuclei while quercetin, an inhibitor of Wnt/β-catenin signaling, completely blocked the effects of LiCl on proliferation. In mice with OIR, intraperitonal or intravitreal treatment with LiCl markedly increased the retinal levels of β-catenin, but did not improve capillary repair. In contrast, repair was significantly improved following intravitreal treatment with Norrin. The effects of LiCl on HDMEC in vitro have minor relevance for OIR in vivo, and the influence of the Norrin/Frizzled-4 pathway on capillary repair in OIR is not reproducible upon enhancing Wnt/β-catenin signaling by LiCl treatment strongly indicating the presence of additional and essential mechanisms.
KW - Animals
KW - Cell Movement/drug effects
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Dermis/blood supply
KW - Endothelial Cells/cytology
KW - Eye Proteins/metabolism
KW - Humans
KW - Indoles/pharmacology
KW - Injections, Intraperitoneal
KW - Lithium Chloride/administration & dosage
KW - Maleimides/pharmacology
KW - Mice
KW - Microvessels/cytology
KW - Neovascularization, Physiologic/drug effects
KW - Nerve Tissue Proteins/metabolism
KW - Oxygen
KW - Retina/drug effects
KW - Vascular Endothelial Growth Factor A/metabolism
KW - Wnt Signaling Pathway/drug effects
U2 - 10.1371/journal.pone.0095546
DO - 10.1371/journal.pone.0095546
M3 - SCORING: Journal article
C2 - 24751879
VL - 9
SP - e95546
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 4
ER -