Deubiquitinase <scp>USP18</scp> regulates reactive astrogliosis by stabilizing <scp>SOX9</scp>

Liu, Wei; Ge, Xuhui; Zhou, Zheng; Jiang, Dongdong; Rong, Yuluo; Wang, Jiaxing; Ji, Chengyue; Fan, Jin; Yin, Guoyong; Cai, Wei

doi:10.1002/glia.23992

Cited by 15 publications

(8 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm these results, we used the neuronal marker NeuN to stain live neurons in specific regions (Z1-Z4), located at indicated distance from the lesion border, in the injured spinal cords of mice in the two groups, as previous described. 34,35 The number of surviving NeuN + neurons in the Z1-Z3 region was significantly higher in the MEVs group than in the EVs group (Figure 2H,I). Collectively, these results indicate that administration of MEVs is more effective in promoting functional behavioral recovery and axonal regeneration post-injury than administration of EVs alone.…”

Section: Administration Of Mevs Promotes Better Functional Behavioral Recovery After Sci In Micementioning

confidence: 96%

“…We established a mouse SCI model in 6-to 8 week-old C57BL/6 mice, as described previously. 35 Briefly, mice were anesthetized by isoflurane inhalation and then subjected to laminectomy to expose the spinal cord at T8. Next, using a spinal cord impactor (RWD Life Science), a rod weighing 5 g was dropped onto the spinal cord from a height of 6.5 cm to induce SCI.…”

Section: Spinal Cord Injury Modelmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular vesicles derived from melatonin‐preconditioned mesenchymal stem cells containing USP29 repair traumatic spinal cord injury by stabilizing NRF2

Liu

Tang

Wang

et al. 2021

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a devastating trauma that leads to irreversible motor and sensory dysfunction and is, so far, without effective treatment. Recently, however, nano-sized extracellular vesicles derived from preconditioned mesenchymal stem cells (MSCs) have shown great promise in treating various diseases, including SCI. In this study, we investigated whether extracellular vesicles (MEVs) derived from MSCs pretreated with melatonin (MT), which is well recognized to be useful in treating diseases, including Alzheimer's disease, non-small cell lung cancer, acute ischemia-reperfusion liver injury, chronic kidney disease, and SCI, are better able to promote functional recovery in mice after SCI than extracellular vesicles derived from MSCs without preconditioning (EVs). MEVs were found to facilitate motor behavioral recovery more than EVs and to increase microglia/macrophages polarization from M1-like to M2like in mice. Experiments in BV2 microglia and RAW264.7 macrophages confirmed that MEVs facilitate M2-like polarization and also showed that they reduce the production of reactive oxygen species (ROS) and regulate mitochondrial function. Proteomics analysis revealed that ubiquitin-specific protease 29 (USP29) was markedly increased in MEVs, and knockdown of USP29 in MEVs (shUSP29-MEVs) abolished MEVs-mediated benefits in vitro and in vivo. We then showed that USP29 interacts with, deubiquitinates and therefore stabilizes nuclear factor-like 2 (NRF2), thereby regulating microglia/macrophages polarization. In NRF2 knockout mice, MEVs failed to promote functional recovery and M2-like microglia/macrophages polarization. We also showed that MT reduced global N6-methyladenosine (m 6 A) modification and levels of the m 6 A "writer" methyltransferase-like 3 (METTL3). The stability of USP29 mRNA in MSCs was enhanced by treatment with MT, but inhibited by overexpression of METTL3.This study describes a very promising extracellular vesicle-based approach for treating SCI.

show abstract

Section: Administration Of Mevs Promotes Better Functional Behavioral Recovery After Sci In Micementioning

confidence: 96%

Section: Spinal Cord Injury Modelmentioning

confidence: 99%

Extracellular vesicles derived from melatonin‐preconditioned mesenchymal stem cells containing USP29 repair traumatic spinal cord injury by stabilizing NRF2

Liu

Tang

Wang

et al. 2021

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ferrostatin-1 alleviated astrocytes inflammation and ferroptosis by suppressing the ROS levels and activating the Nrf2/HO-1 signaling pathway (Li S. et al, 2021 ). Additionally, many other molecules, such as USP18 (Liu W. et al, 2021 ), p-ERK1/2 (Li et al, 2021a ), CREB (Pardo et al, 2016 ), HSPA12B (Xia et al, 2016 ), CCR5 (Joy et al, 2019 ), also represent potential therapeutic targets that merit further investigation.…”

Section: Strategies For Astrocyte-targeted Therapymentioning

confidence: 99%

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Zhang

Ning

2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Traumatic central nervous system (CNS) injury, which includes both traumatic brain injury (TBI) and spinal cord injury (SCI), is associated with irreversible loss of neurological function and high medical care costs. Currently, no effective treatment exists to improve the prognosis of patients. Astrocytes comprise the largest population of glial cells in the CNS and, with the advancements in the field of neurology, are increasingly recognized as having key functions in both the brain and the spinal cord. When stimulated by disease or injury, astrocytes become activated and undergo a series of changes, including alterations in gene expression, hypertrophy, the loss of inherent functions, and the acquisition of new ones. Studies have shown that astrocytes are highly heterogeneous with respect to their gene expression profiles, and this heterogeneity accounts for their observed context-dependent phenotypic diversity. In the inured CNS, activated astrocytes play a dual role both as regulators of neuroinflammation and in scar formation. Identifying the subpopulations of reactive astrocytes that exert beneficial or harmful effects will aid in deciphering the pathological mechanisms underlying CNS injuries and ultimately provide a theoretical basis for the development of effective strategies for the treatment of associated conditions. Following CNS injury, as the disease progresses, astrocyte phenotypes undergo continuous changes. Although current research methods do not allow a comprehensive and accurate classification of astrocyte subpopulations in complex pathological contexts, they can nonetheless aid in understanding the roles of astrocytes in disease. In this review, after a brief introduction to the pathology of CNS injury, we summarize current knowledge regarding astrocyte activation following CNS injury, including: (a) the regulatory factors involved in this process; (b) the functions of different astrocyte subgroups based on the existing classification of astrocytes; and (c) attempts at astrocyte-targeted therapy.

show abstract

“…Analyses of footprints were performed as previously mentioned [ 46 ]. The mouse's anterior and posterior limbs were dyed blue and red, respectively, and only when they ran at a steady velocity were stride lengths and widths measured.…”

Section: Methodsmentioning

confidence: 99%

Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury

et al. 2022

Self Cite

View full text Add to dashboard Cite

Neuroinflammation is an important cause of poor prognosis in patients with spinal cord injury. pyroptosis is a new type of inflammatory cell death. Treg cells has been shown to play an anti-inflammatory role in a variety of inflammatory diseases, including inflammatory bowel disease, amyotrophic lateral sclerosis, and arthritis. However, little is known about Treg cells' potential role in pyroptosis following spinal cord injury. The aim of this research was to look into the effect of Treg cells to motor function recovery, pyroptosis and the mechanism behind it after SCI. Here, we found that pyroptosis mainly occurred in microglia on the seventh day after spinal cord injury. Konckout Treg cells resulted in widely pyroptosis and poor motor recovery after SCI. In conversely, over-infiltration of Treg cell in mice by tail vein injection had beneficial effects following SCI.Treg cell-derived exosomes promote functional recovery by inhibiting microglia pyroptosis in vivo. Bioinformatic analysis revealed that miRNA-709 was significantly enriched in Treg cells and Treg cell-secreted exosomes. NKAP has been identified as a miRNA-709 target gene. Moreover, experiments confirmed that Treg cells targeted the NKAP via exosomal miR-709 to reduce microglia pyroptosis and promote motor function recovery after SCI. More importantly, The miR-709 overexpressed exosomes we constructed significantly reduced the inflammatory response and improved motor recovery after spinal cord injury. In brief, our findings indicate a possible mechanism for communication between Treg cells and microglia, which opens up a new perspective for alleviating neuroinflammation after SCI.

show abstract

Deubiquitinase USP18 regulates reactive astrogliosis by stabilizing SOX9

Cited by 15 publications

References 55 publications

Extracellular vesicles derived from melatonin‐preconditioned mesenchymal stem cells containing USP29 repair traumatic spinal cord injury by stabilizing NRF2

Extracellular vesicles derived from melatonin‐preconditioned mesenchymal stem cells containing USP29 repair traumatic spinal cord injury by stabilizing NRF2

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury

Contact Info

Product

Resources

About