All-Trans Retinoic Acid–Preconditioned Mesenchymal Stem Cells Improve Motor Function and Alleviate Tissue Damage After Spinal Cord Injury by Inhibition of HMGB1/NF-κB/NLRP3 Pathway Through Autophagy Activation

Gholaminejhad, Morteza; Jameie, Seyed Behnamedin; Abdi, Mahdad; Abolhassani, Farid; Mohammed, Ibrahim; Hassanzadeh, Gholamreza

doi:10.1007/s12031-022-01977-0

Cited by 12 publications

(18 citation statements)

References 89 publications

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“…Morteza demonstrated that the HMGB1/Nuclear factor of κB (NF-κB) signaling pathway was activated after SCI. Downregulation of the levels of HMGB1 and p-NF-κB suppressed the secondary phase SCI injuries in rats [16].…”

Section: Introductionmentioning

confidence: 93%

Downregulation of High mobility group box 2 relieves spinal cord injury by inhibiting microglia-mediated neuroinflammation

Yang

Chen

et al. 2023

Exp. Anim.

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Spinal cord injury (SCI), characterized by sensory disturbance and motor deficits, is associated with excessive inflammatory cytokine production of microglial cells.Previous studies have demonstrated High mobility group box 2 (HMGB2) as a microglial pro-inflammatory factor in stroke. This present study aims to evaluate the function of HMGB2 in a SCI rat model induced by striking the spinal cord at T9 to T12 using a rod. Our results showed that the levels of HMGB2 were significantly increased in the spinal cord tissues of SCI rats. Besides, HMGB2 downregulation was achieved by receiving an injection of lentivirus encoding HMGB2 shRNA in the spinal cord. Knockdown of HMGB2 suppressed SCI-induced microglial activation and neuroinflammation, as well as alleviated neuronal loss. In addition, we confirmed that HMGB2 silencing lessened lipopolysaccharide (LPS)-induced neuroinflammation in BV-2 cells. Furthermore, our findings demonstrated that HMGB2 knockdown suppressed the canonical nuclear factor of kB (NF-κB) signaling pathway both in vivo and in vitro. Collectively, this study manifested strong anti-inflammatory roles of HMGB2 knockdown on microglia-mediated neuroinflammation and suggested that HMGB2 might serve as a potential target for SCI therapy.

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Section: Introductionmentioning

confidence: 93%

Downregulation of High mobility group box 2 relieves spinal cord injury by inhibiting microglia-mediated neuroinflammation

Yang

Chen

et al. 2023

Exp. Anim.

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“…ATRA-MSC therapy was shown to have significant therapeutic effects on the injured spinal cord and regulate excessive neuroinflammation via inhibiting the NLRP3 inflammasome pathway and activating autophagy. 166 A homeostatic mechanism known as autophagy, which is a cellular process that removes unnecessary or damaged components in a lysosome-dependent manner, is activated in a number of pathological conditions such as inflammation, cancer, and neurodegenerative diseases. 167 A proper balance between the essential innate inflammatory responses and the avoidance of uncontrolled inflammation is achieved by autophagy and inflammasome interplay.…”

Section: Mscs and Their Exosomes Alleviate Cns Diseases By Targeting ...mentioning

confidence: 99%

Mesenchymal stem cells (MSCs) and MSC‐derived exosomes in animal models of central nervous system diseases: Targeting the NLRP3 inflammasome

et al. 2023

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The NLRP3 (NOD‐, LRR‐, and pyrin domain‐containing protein 3) inflammasome is a multimeric protein complex that is engaged in the innate immune system and plays a vital role in inflammatory reactions. Activation of the NLRP3 inflammasome and subsequent release of proinflammatory cytokines can be triggered by microbial infection or cellular injury. The NLRP3 inflammasome has been implicated in the pathogenesis of many disorders affecting the central nervous system (CNS), ranging from stroke, traumatic brain injury, and spinal cord injury to Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, and depression. Furthermore, emerging evidence has suggested that mesenchymal stem cells (MSCs) and their exosomes may modulate NLRP3 inflammasome activation in a way that might be promising for the therapeutic management of CNS diseases. In the present review, particular focus is placed on highlighting and discussing recent scientific evidence regarding the regulatory effects of MSC‐based therapies on the NLRP3 inflammasome activation and their potential to counteract proinflammatory responses and pyroptotic cell death in the CNS, thereby achieving neuroprotective impacts and improvement in behavioral impairments.

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“…SCI is characterized by sensory, motor and autonomic nerve dysfunction ( 16 ) mediated by complex and diverse pathophysiological processes, including neuroinflammation, neuronal death, glial scar formation and axonal regeneration ( 17 – 20 ). The concentration of HMGB1 in the injured area increases rapidly and lasts for a long time ( 21 – 31 ), and it not only aggravates injury by playing the role of an inflammatory cytokine, but it also promotes the recovery of the injured spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Review: The role of HMGB1 in spinal cord injury

Chen

2023

Front. Immunol.

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High mobility group box 1 (HMGB1) has dual functions as a nonhistone nucleoprotein and an extracellular inflammatory cytokine. In the resting state, HMGB1 is mainly located in the nucleus and regulates key nuclear activities. After spinal cord injury, HMGB1 is rapidly expressed by neurons, microglia and ependymal cells, and it is either actively or passively released into the extracellular matrix and blood circulation; furthermore, it also participates in the pathophysiological process of spinal cord injury. HMGB1 can regulate the activation of M1 microglia, exacerbate the inflammatory response, and regulate the expression of inflammatory factors through Rage and TLR2/4, resulting in neuronal death. However, some studies have shown that HMGB1 is beneficial for the survival, regeneration and differentiation of neurons and that it promotes the recovery of motor function. This article reviews the specific timing of secretion and translocation, the release mechanism and the role of HMGB1 in spinal cord injury. Furthermore, the role and mechanism of HMGB1 in spinal cord injury and, the challenges that still need to be addressed are identified, and this work will provide a basis for future studies.

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All-Trans Retinoic Acid–Preconditioned Mesenchymal Stem Cells Improve Motor Function and Alleviate Tissue Damage After Spinal Cord Injury by Inhibition of HMGB1/NF-κB/NLRP3 Pathway Through Autophagy Activation

Cited by 12 publications

References 89 publications

Downregulation of High mobility group box 2 relieves spinal cord injury by inhibiting microglia-mediated neuroinflammation

Downregulation of High mobility group box 2 relieves spinal cord injury by inhibiting microglia-mediated neuroinflammation

Mesenchymal stem cells (MSCs) and MSC‐derived exosomes in animal models of central nervous system diseases: Targeting the NLRP3 inflammasome

Review: The role of HMGB1 in spinal cord injury

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