1. Differential angiogenic properties of lithium chloride in vitro and in vivo
- Author
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Ohlmann, Andreas, Tamm, Ernst R., Knobloch, Verena, Müller, Birgit, and Zeilbeck, Ludwig Franz
- Subjects
Vascular Endothelial Growth Factor A ,Indoles ,Cell Survival ,Neovascularization, Physiologic ,lcsh:Medicine ,Mouse Models ,Nerve Tissue Proteins ,Research and Analysis Methods ,Epithelium ,Retina ,Maleimides ,Catenin Signal Transduction ,Mice ,Model Organisms ,Cell Signaling ,Ocular System ,Cell Movement ,Molecular Cell Biology ,Medicine and Health Sciences ,Animals ,Humans ,570 Biowissenschaften, Biologie ,Eye Proteins ,lcsh:Science ,Wnt Signaling Pathway ,WNT Signaling Cascade ,Cell Proliferation ,lcsh:R ,Biology and Life Sciences ,Endothelial Cells ,Epithelial Cells ,Cell Biology ,Animal Models ,Dermis ,Beta-Catenin Signaling ,Signaling Cascades ,Oxygen ,Ophthalmology ,Biological Tissue ,Microvessels ,Retinal Disorders ,lcsh:Q ,ddc:570 ,Anatomy ,Cellular Types ,Lithium Chloride ,Injections, Intraperitoneal ,Research Article ,Signal Transduction - Abstract
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.
- Published
- 2014
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