Transglutaminase 2 Prevents Premature Senescence and Promotes Osteoblastic Differentiation of Mesenchymal Stem Cells through NRF2 Activation.

Transglutaminase 2 (TG2) is a multifunctional enzyme that exhibits transamidase, GTPase, kinase, and protein disulfide isomerase (PDI) activities. Of these, transamidase-mediated modification of proteins regulates apoptosis, differentiation, inflammation, and fibrosis. TG2 is highly expressed in mesenchymal stem cells (MSCs) compared with differentiated cells, suggesting a role of TG2 specific for MSC characteristics.

Double-Stranded RNA Enhances Matrix Metalloproteinase-1 and -13 Expressions through TLR3-Dependent Activation of Transglutaminase 2 in Dermal Fibroblasts.

UV-irradiation induces the secretion of double-stranded RNA (dsRNA) derived from damaged noncoding RNAs in keratinocytes, which enhance the expression of matrix metalloproteinases (MMP) in non-irradiated dermal fibroblasts, leading to dysregulation of extracellular matrix homeostasis. However, the signaling pathway responsible for dsRNA-induced MMP expression has not been fully understood. Transglutaminase 2 (TG2) is an enzyme that modifies substrate proteins by incorporating polyamine or crosslinking of proteins, thereby regulating their functions.

An Effective Method to Reduce Residual Lithium on LiNiCoMnO₂ Cathode Material Using a Reducing Agent.

Among the various cathode materials used in LIBs (Lithium ion batteries), nickel rich cathode materials have attracted an increasing amount of interest due to their high capacity, relatively low cost, and low toxicity when compared to LiCoO₂. However, these materials always contain a large amount of residual lithium compounds such as LiOH and Li₂CO₃. The presence of lithium residues is undesirable because the oxidation of these compounds results in the formation of Li₂O and CO₂ gas at higher voltages, which lowers the coulombic efficiency between the charge and discharge capacities during cycling.

Glutathione dynamics determine the therapeutic efficacy of mesenchymal stem cells for graft-versus-host disease via CREB1-NRF2 pathway.

Glutathione (GSH), the most abundant nonprotein thiol functioning as an antioxidant, plays critical roles in maintaining the core functions of mesenchymal stem cells (MSCs), which are used as a cellular immunotherapy for graft-versus-host disease (GVHD). However, the role of GSH dynamics in MSCs remains elusive. Genome-wide gene expression profiling and high-throughput live-cell imaging assays revealed that CREB1 enforced the GSH-recovering capacity (GRC) of MSCs through NRF2 by directly up-regulating NRF2 target genes responsible for GSH synthesis and redox cycling.

Keratinocyte transglutaminase 2 promotes CCR6 γδT-cell recruitment by upregulating CCL20 in psoriatic inflammation.

Keratinocyte-derived cytokines and chemokines amplify psoriatic inflammation by recruiting IL-17-producing CCR6 γδT-cells and neutrophils. The expression of these cytokines and chemokines mainly depends on NF-κB activity; however, the pathway that activates NF-κB in response to triggering factors is poorly defined. Here, we show that transglutaminase 2 (TG2), previously reported to elicit a T17 response by increasing IL-6 expression in a mouse model of lung fibrosis, mediates the upregulation of cytokines and chemokines by activating NF-κB in imiquimod (IMQ)-treated keratinocytes.

Transglutaminase 2 mediates hypoxia-induced selective mRNA translation via polyamination of 4EBPs.

Hypoxia selectively enhances mRNA translation despite suppressed mammalian target of rapamycin complex 1 activity, contributing to gene expression reprogramming that promotes metastasis and survival of cancer cells. Little is known about how this paradoxical control of translation occurs. Here, we report a new pathway that links hypoxia to selective mRNA translation.

Competitive Binding of Magnesium to Calcium Binding Sites Reciprocally Regulates Transamidase and GTP Hydrolysis Activity of Transglutaminase 2.

Transglutaminase 2 (TG2) is a Ca-dependent enzyme, which regulates various cellular processes by catalyzing protein crosslinking or polyamination. Intracellular TG2 is activated and inhibited by Ca and GTP binding, respectively. Although aberrant TG2 activation has been implicated in the pathogenesis of diverse diseases, including cancer and degenerative and fibrotic diseases, the structural basis for the regulation of TG2 by Ca and GTP binding is not fully understood.

Effect of PEDOT:PSS (Poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate) Coating on Nanostructured Cobalt-Free LiNiMnO₂ Layered Oxide Cathode Materials for Lithium-Ion Battery.

Among cobalt-free layered oxides, Li(NiMn)O₂ ( ≤0.5) (LNMO) shows high reversible capacity, good cycling performance and thermal stability, and has relatively low cost and toxicity due to the absence of cobalt. In this study, we synthesized LNMO cathode materials having a porous fiber shape with primary particles that had an average diameter of about 328 nm.

Novel Composition of Co-Free LiNiMnAlO₂ Cathode Materials.

Ni-rich LiNiMnO₂ cathode materials have attracted widespread interest as promising alternative cathode materials owing to their higher capacity, lower cost, and lower toxicity compared to those of LiCoO₂. Therefore, we designed herein a LiNiMnO₂ positive electrode material. However, as the Ni content increases, the materials suffer from an extensive phase transition during the de-lithiation process owing to the low-bond strength of Ni (391.

Monitoring Glutathione Dynamics and Heterogeneity in Living Stem Cells.

Glutathione (GSH) is a major antioxidant in cells, and plays vital roles in the cellular defense against oxidants and in the regulation of redox signals. In a previous report, we demonstrated that stem cell function is critically affected by heterogeneity and dynamic changes in cellular GSH concentration. Here, we present a detailed protocol for the monitoring of GSH concentration in living stem cells using FreSHtracer, a real-time GSH probe.

Novel Core-Shell-Type Design of Na[Li(NiCoMn)(Ni CoMn)]O₂ Cathode Material for Sodium-Ion Batteries.

High-nickel cathode materials possess several disadvantages such as poor cycle performance and thermal instability resulting from the side reaction with the electrolyte that occurs during cycling. In order to improve the cycle performance and thermal stability of the Na[Li(NiCoMn)]O₂ (core), we synthesized the core-shell structure of Na[Li(NiCoMn)(NiCoMn)]O₂. The results of energy-dispersive X-ray spectroscopy (EDS) line analysis showed that the core of the high-nickel NCM precursor and the shell of the low-nickel NCM precursor were successfully synthesized as two phases.

Real-Time Monitoring of Glutathione in Living Cells Reveals that High Glutathione Levels Are Required to Maintain Stem Cell Function.

The core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered by lack of probe.

Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production.

UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report a novel role of transglutaminase 2 (TG2), a member of the TG enzyme family whose activities are critical for cornified envelope formation, in mediating UV-induced inflammation.

Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells.

Bone morphogenetic proteins (BMPs) that belong to the transforming growth factor-β (TGF-β) superfamily cytokines, play crucial roles in hematopoiesis. However, roles of Smad6 in hematopoiesis remained unknown in contrast to the other inhibitory Smad (I-Smad), Smad7. Here we show that Smad6 inhibits erythropoiesis in human CD34(+) cord blood hematopoietic stem cells (HSCs).

Combined effects of hematopoietic progenitor cell mobilization from bone marrow by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the brain using stromal cell-derived factor-1α in an Alzheimer's disease mouse model.

Transplantation of bone marrow-derived stem cells (BMSCs) has been suggested as a potential therapeutic approach to prevent neurodegenerative diseases, but it remains problematic due to issues of engraftment, potential toxicities, and other factors. An alternative strategy is pharmacological-induced recruitment of endogenous BMSCs into an injured site by systemic administration of growth factors or chemokines. Therefore, the aim of this study was to examine the effects of therapy involving granulocyte colony stimulating factor (G-CSF)/AMD3100 (CXCR4 antagonist) and stromal cell-derived factor-1α (SDF-1α) on endogenous BM-derived hematopoietic progenitor cell (BM-HPC) recruitment into the brain of an Alzheimer's disease (AD) mouse model.

The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.

The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD.