The role of PI3K/Akt signalling pathway in spinal cord injury

Xiao, Chun-Lin; Yin, Wenchao; Zhong, Yanqiang; Luo, Jia-Quan; Liu, Lulin; Liu, Wu-Yang; Zhao, Kai

doi:10.1016/j.biopha.2022.113881

Cited by 36 publications

(15 citation statements)

References 176 publications

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“…The PI3K/Akt signaling pathway plays a key regulatory role in neuronal cell survival and is involved in promoting SCI repair. 48,49 Studies have confirmed a close relationship between the Nrg-1/ErbB signaling pathway and neuronal demyelination, growth, development, and protection after injury. 50 Differentially expressed miRNAs and proteins in SCA-Exo were associated with the VEGF signaling pathway, VEGFactivated receptor activity, and angiogenesis.…”

Section: ■ Results and Discussionmentioning

confidence: 95%

Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote In Situ Centralis Neuroplasticity

Chang

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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Spinal cord injury (SCI), one of the most serious injuries of the central nervous system, causes physical functional dysfunction and even paralysis in millions of patients. As a matter of necessity, redressing the neuroleptic pathologic microenvironment to a neurotrophic microenvironment is essential in order to alleviate this dilemma and facilitate the recovery of the spinal cord. Herein, based on cell-sheet technology, two functional cell types�uninduced and neural-induced stem cells from human exfoliated deciduous teeth�were formed into a composite membrane that subsequently self-assembled to form a bioactive scaffold with a spinal-cord-like structure, called a spinal cord assembly (SCA). In a stable extracellular matrix microenvironment, SCA continuously released SCA-derived exosomes containing various neurotrophic factors, which effectively promoted neuronal regeneration, axonal extension, and angiogenesis and inhibited glial scar generation in a rat model of SCI. Neurotrophic exosomes significantly improved the pathological microenvironment and promoted in situ centralis neuroplasticity, ultimately eliciting a strong repair effect in this model. SCA therapy is a promising strategy for the effective treatment of SCI based on neurotrophic exosome delivery.

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Section: ■ Results and Discussionmentioning

confidence: 95%

Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote In Situ Centralis Neuroplasticity

Chang

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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“…Other underlying mechanisms for OPN's neuroprotective role may include suppressing inflammation and apoptosis through AKT activation. 42 Further examination is required to delineate VEGF and AKT's exact contribution to OPN's neuroprotective mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…OPN could promote angiogenesis through VEGF and/or AKT pathways, 40,41 as we detected potential modulation of VEGF and AKT phosphorylation mediated by OPN post-SCI in this study. Other underlying mechanisms for OPN’s neuroprotective role may include suppressing inflammation and apoptosis through AKT activation 42 . Further examination is required to delineate VEGF and AKT’s exact contribution to OPN’s neuroprotective mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain after Spinal Cord Injury

Weng,

Lu,

et al. 2024

Spine

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Study Design. Basic science study using a hemi-section spinal cord injury (SCI) model. Objective. We sought to assess the effect of blocking Osteopontin (OPN) up-regulation on motor function recovery and pain behavior after SCI and to further investigate the possible downstream target of OPN in the injured spinal cord. Summary of Background Data. OPN is a noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous study suggested that this protein might contribute to locomotor function recovery after SCI. However, its neuroprotective potential was not fully explored, nor were the underlying mechanisms. Methods. We constructed a SCI mouse model and analyzed the expression of OPN at different time points, and the particular cell distribution in the injured spinal cord. Then, we blocked OPN up-regulation with lentivirus delivering siRNA targeting OPN specifically and examined its effect on motor function impairment and neuropathic pain after SCI. The underlying mechanisms were explored in the OPN-knockdown mice model and cultured vascular endothelial cells. Results. The proteome study revealed that OPN was the most dramatically increased protein following SCI. OPN in the spinal cord was increased significantly 3 weeks after SCI. Suppressing the OPN up-regulation via siRNA exacerbated motor function impairment and neuropathic pain. Additionally, SCI resulted in an increase in the vascular endothelial growth factor (VEGF), AKT phosphorylation, and angiogenesis within the spinal cord, all of which were curbed by OPN reduction. Similarly, OPN knockdown suppressed VEGF expression, AKT phosphorylation, cell migration, invasion, and angiogenesis in cultured vascular endothelial cells. Conclusion. OPN demonstrates a protective influence against motor function impairment and neuropathic pain following SCI. This phenomenon may result from the pro-angiogenetic effect of OPN, possibly due to activation of the VEGF and/or AKT pathways.

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“…Dysregulation of the PI3K/Akt signaling pathway is seen in a variety of human diseases, including cancer, diabetes, cardiovascular diseases, and neurological diseases, while dysregulation of Akt signaling contributes to an increased frequency of human diseases. [3][4][5][6] Another study pointed out that the PI3K-Akt signaling pathway is an important pathway that mediates the pro-survival of multiple growth factors. [7] Based on the herbal-disease-target network analysis, the key ingredients were ranked by degree value, and those with a greater than average degree value were selected as the key active ingredients.…”

Section: Discussionmentioning

confidence: 99%

Elucidating the mechanism of Hongjinshen decoction in the treatment of pulmonary fibrosis based on network pharmacology and molecular docking

Chen

Zeng

et al. 2022

Medicine

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Background: To explore the mechanism of compound Hongginshen decoction in improving pulmonary fibrosis based on network pharmacology. Methods: The active components and targets of ginseng and Salvia miltiorrhiza were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The chemical components of Rhodiola, Ophiopogon japonicus, and Dendrobium were screened using the Traditional Chinese Medicine Integrated Database (TCMID), and the target compounds were predicted by the Swisstargets method. The related target genes of pulmonary fiber (PF) were screened by the Genecards database and the National Center of Biotechnology Information (NCBI) database. The protein–protein interaction network was drawn using the string database and Cytoscape software, and the network topology was analyzed. Then, using R3.6.3 software, biological processes, molecular function, cell component enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out on the common targets of drugs and diseases. The network diagram of the “traditional Chinese medicine composition disease target” of Compound Hongginshen Decoction was constructed and analyzed with the software of Cytoscape 3.6.1. Results: We identified 159 active components and 2820 targets in Compound Hongginshen Decoction, and 2680 targets in pulmonary fibrosis. A total of 343 common targets were obtained by the intersection of drug targets and disease targets. protein–protein interaction protein interaction network analysis showed that PIK3CA, PIK3R1, MAPK1, SRC, AKT1, and so on may be the core targets of the compound Hongjingshen recipe in the treatment of pulmonary fibrosis. Gene Ontology (GO) enrichment analysis identified 3463 items, and KEGG pathway enrichment analysis identified 181 related signaling pathways, including the PI3K-Akt signaling pathway, HCMV pathway, Hb pathway, PGs pathway, and KSHV signaling pathway. Conclusion: Compound Hongginshen Decoction has the characteristics of a multichannel and multitargeted effect in the treatment of pulmonary fibrosis. Radix Ophiopogonis and Dendrobium officinale play a key role in the treatment of pulmonary fibrosis. The whole compound prescription may play a therapeutic role by affecting cell metabolism, being anti-inflammatory, regulating the immune system, promoting angiogenesis, and improving anaerobic metabolism.

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The role of PI3K/Akt signalling pathway in spinal cord injury

Cited by 36 publications

References 176 publications

Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote In Situ Centralis Neuroplasticity

Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote In Situ Centralis Neuroplasticity

Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain after Spinal Cord Injury

Elucidating the mechanism of Hongjinshen decoction in the treatment of pulmonary fibrosis based on network pharmacology and molecular docking

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