Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3- independent mechanism

Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy

“…63,64 Our data suggest that lithium's vascular effects were likely mediated primarily through activation of the Wnt signaling pathway, by inhibiting the secondary Wnt signaling complex containing GSK3b, thus stabilizing the downstream factor b-catenin to eventually promote vascular formation. However, it is not clear whether potential Wnt/GSK3-independent effects of lithium may also be at work, including those through inositol depletion, 65 bone morphogenetic protein (BMP)-2 signaling, 66 transcription factor 7-like 2 gene RNA splicing, 67 or mitogenactivated protein (MAP) extracellular signal-related kinase (ERK) kinase (MEK)-ERK pathway. 68 In addition, direct neuronal effects of lithium are also possible because lithium was found to protect neurons and to promote synaptic formation.…”

GSK-3β inhibition protects mesothelial cells during experimental peritoneal dialysis through upregulation of the heat shock response

“…Lithium has been reported to be a selective inhibitor of GSK-3β catalytic activity by competition for magnesium (Ryves et al 2002) and to indirectly increase inhibitory phosphorylation of GSK-3β (De Sarno et al 2002). We decided to focus on LiCl as this compound is broadly investigated as standard GSK-3β inhibitor both in clinical and experimental research (Carmichael et al 2002;Chuang et al 2011;Li et al 2011). In our study, LiCl was found to be most effective at concentrations of 10 mM, which is the dose used in the majority of in vitro studies (Lewitt et al 2001;Mantelli and Ledda 1989;Gregory et al 2005;Lucas et al 2010;Li et al 2011).…”

“…We decided to focus on LiCl as this compound is broadly investigated as standard GSK-3β inhibitor both in clinical and experimental research (Carmichael et al 2002;Chuang et al 2011;Li et al 2011). In our study, LiCl was found to be most effective at concentrations of 10 mM, which is the dose used in the majority of in vitro studies (Lewitt et al 2001;Mantelli and Ledda 1989;Gregory et al 2005;Lucas et al 2010;Li et al 2011). Indeed, addition of lithium to the cytotoxic PDF Dianeal® and Extraneal® prior to experimental PD resulted in significant cytoprotection of the exposed mesothelial cells, as reflected by several assessments of cellular viability, such as dose-dependent decrease of LDH release, reduced cell death rate in the live/dead assay and improved cell survival measured as neutral red uptake.…”

“…Albeit such ex vivo exposure to diluted PDF still represents an artificial system, this model likely reflects intraperitoneal conditions more closely to those prevalent during an intraperitoneal PD dwell and has been previously shown to be relevant to assess the balance of mesothelial cell injury and repair processes (Mantelli and Ledda 1989;Li et al 2011;Ring et al 2003;Kratochwill et al 2012). Confirming the data of acute PDF exposure in the MeT-5A mesothelial cell line, the addition of lithium to PDF resulted in increased levels of phospho-GSK-3β-reflecting inhibition of GSK-3β activation-and in decreased cellular damage in peritoneal effluent-derived primary mesothelial cells.…”

“…Lithium chloride (LiCl) was added for dose-response experiments in concentrations from 1 to 10 mM; for the remaining experiments, LiCl was administered at a concentration of 10 mM which is in the dose range that is applied in most in vitro studies (Lewitt et al 2001;Mantelli and Ledda 1989;Gregory et al 2005;Lucas et al 2010;Li et al 2011). LiCl treatment was started 24 h prior to incubation with PDF and was applied during the whole experiment.…”