Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice

Tanabe, Norio; Kuboyama, Tomoharu; Tohda, Chihiro

doi:10.3389/fphar.2018.00446

Cited by 27 publications

(9 citation statements)

References 45 publications

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“…As a result, resistance against proteolysis is changed. Using this method, many ligand and receptor pairs have been identified ( Qu et al, 2016 ; Yang et al, 2017 ; Tanabe et al, 2018 ). In the current study, cell lysate of astrocytes was incubated with recombinant NLK or vehicle.…”

Section: Resultsmentioning

confidence: 99%

“…It has not been clarified whether NLK decreases CSPGs levels at the lesion site. We previously reported that several agents showed axonal growth activity without the alteration at the lesion site ( Teshigawara et al, 2013 ; Tanabe et al, 2018 ). From our in vitro experiment (Figure 2D ), NLK promoted axonal growth in the presence of CSPG.…”

Section: Discussionmentioning

confidence: 99%

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Extracellular Neuroleukin Enhances Neuroleukin Secretion From Astrocytes and Promotes Axonal Growth in vitro and in vivo

et al. 2018

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Under pathological conditions in the central nervous system (CNS), including spinal cord injury, astrocytes show detrimental effects against neurons. It is also known that astrocytes sometimes exert beneficial effects, such as neuroprotection and secretion of axonal growth factors. If beneficial effects of astrocytes after injury could be induced, dysfunction of the injured CNS may improve. However, a way of promoting beneficial functions in astrocytes has not been elucidated. In the current study, we focused on neuroleukin (NLK), which is known to have axonal growth activities in neurons. Although NLK is secreted from astrocytes, the function of NLK in astrocytes is poorly understood. We aimed to clarify the mechanism of NLK secretion in astrocytes and the functional significance of secreted NLK from astrocytes. Stimulation of cultured astrocytes with recombinant NLK significantly elevated the secretion of NLK from astrocytes. Furthermore, astrocyte conditioned medium treated with NLK increased axonal density in cultured cortical neurons. Recombinant NLK itself directly increased axonal density in cultured neurons. These results indicated that NLK secreted from astrocytes acted as an axonal growth factor and that secretion was stimulated by extracellular NLK. To elucidate a direct binding molecule of NLK on astrocytes, drug affinity responsive target stability (DARTS) analysis was performed. A 78 kDa glucose regulated protein (GRP78) was identified as a receptor for NLK, which was related to the secretion of NLK from astrocytes. When NLK was injected into the lesion site of spinal cord injured mice, axonal density in the injured region was significantly increased and hindlimb motor function improved. These results suggested that NLK-GRP78 signalling was important for the beneficial effects of astrocytes. This study strengthens the potential of astrocytes for use as therapeutic targets in CNS traumatic injury.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Extracellular Neuroleukin Enhances Neuroleukin Secretion From Astrocytes and Promotes Axonal Growth in vitro and in vivo

et al. 2018

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“…Though not a large number of differential m6A genes are identified, many of which are related to neural injury and repair. For instance, HSP90 participates in axonal regeneration and functional recovery after SCI (Takata et al., 2003; Tanabe et al., 2018). Lama2 released from the CNS resident pericytes can enhance oligodendrocyte progenitor cell differentiation and thus promote CNS remyelination (De La Fuente et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Epitranscriptomic m6A regulation following spinal cord injury

Xing

Cai

Yang

et al. 2020

J of Neuroscience Research

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RNA methylation is involved in multiple physiological and pathological processes. However, the role of RNA methylation in spinal cord regeneration has not been reported. In this study, we find an altered m6A (N6-methyladenosine) RNA methylation profiling following zebrafish spinal cord injury (SCI), in line with an altered transcription level of the m6A methylase Mettl3. Interestingly, many of the differential m6A-tagged genes associated with neural regeneration are hypomethylated, but their transcription levels are upregulated in SCI. Moreover, we find that METTL3 may be important for spinal cord regeneration. We also show a conserved feature of METTL3 changes in mouse SCI model, in which the expression of METTL3 is increased in both astrocytes and neural stem cells. Together, our results indicate that m6A RNA methylation is dynamic and conserved following SCI and may contribute to spinal cord regeneration.

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“…Through drug affinity response target stability (DARTS) system screening, Matrine can directly bind heat shock protein 90 (HSP90), through neutralization. Specific blockade of anti-HSP90 by antibody can inhibit the growth of axons induced by matrine, suggesting that the improvement of SCI by matrine depends on the regulation of HSP90 (Tanabe et al, 2018). Matrine can also upregulate the expression of protein lipid protein, increase the number of…”

Section: Spinal Cord Injury/encephalomyelitismentioning

confidence: 99%

Matrine: A Promising Natural Product With Various Pharmacological Activities

et al. 2020

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Matrine is an alkaloid isolated from the traditional Chinese medicine Sophora flavescens Aiton. At present, a large number of studies have proved that matrine has an anticancer effect can inhibit cancer cell proliferation, arrest cell cycle, induce apoptosis, and inhibit cancer cell metastasis. It also has the effect of reversing anticancer drug resistance and reducing the toxicity of anticancer drugs. In addition, studies have reported that matrine has a therapeutic effect on Alzheimer's syndrome, encephalomyelitis, asthma, myocardial ischemia, rheumatoid arthritis, osteoporosis, and the like, and its mechanism is mainly related to the inhibition of inflammatory response and apoptosis. Its treatable disease spectrum spans multiple systems such as the nervous system, circulatory system, and immune system. The antidisease effect and mechanism of matrine are diverse, so it has high research value. This review summarizes recent studies on the pharmacological mechanism of matrine, with a view to providing reference for subsequent research.

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Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice

Cited by 27 publications

References 45 publications

Extracellular Neuroleukin Enhances Neuroleukin Secretion From Astrocytes and Promotes Axonal Growth in vitro and in vivo

Extracellular Neuroleukin Enhances Neuroleukin Secretion From Astrocytes and Promotes Axonal Growth in vitro and in vivo

Epitranscriptomic m6A regulation following spinal cord injury

Matrine: A Promising Natural Product With Various Pharmacological Activities

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