ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

Xia, Wenzheng; Zhu, Jin; Wang, Xueyi; Tang, Yinda; Zhou, Ping; Hou, Meng; Li, Shiting

doi:10.1096/fj.202000726rrr

Cited by 25 publications

(18 citation statements)

References 49 publications

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“…AnxA1 acts as the extracellular trigger for SC proliferation and migration, and activates FPR2 and the downstream adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) inflammatory signaling cascade. AMPK phosphorylation induced by insulin-like growth factor-1 improves the mitochondrial function to drive axonal outgrowth, therefore promoting the SC proliferation and nerve regeneration ( Xia et al, 2020 ).…”

Section: Formyl Peptide Receptor Action In Neuroinflammationmentioning

confidence: 99%

The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation

Zhu

Ding

et al. 2021

Front. Cell. Neurosci.

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Formyl peptide receptors (FPRs) are a group of G protein-coupled cell surface receptors that play important roles in host defense and inflammation. Owing to the ubiquitous expression of FPRs throughout different cell types and since they interact with structurally diverse chemotactic agonists, they have a dual function in inflammatory processes, depending on binding with different ligands so that accelerate or inhibit key intracellular kinase-based regulatory pathways. Neuroinflammation is closely associated with the pathogenesis of neurodegenerative diseases, neurogenic tumors and cerebrovascular diseases. From recent studies, it is clear that FPRs are important biomarkers for neurological diseases as they regulate inflammatory responses by monitoring glial activation, accelerating neural differentiation, regulating angiogenesis, and controlling blood brain barrier (BBB) permeability, thereby affecting neurological disease progression. Given the complex mechanisms of neurological diseases and the difficulty of healing, we are eager to find new and effective therapeutic targets. Here, we review recent research about various mechanisms of the effects generated after FPR binding to different ligands, role of FPRs in neuroinflammation as well as the development and prognosis of neurological diseases. We summarize that the FPR family has dual inflammatory functional properties in central nervous system. Emphasizing that FPR2 acts as a key molecule that mediates the active resolution of inflammation, which binds with corresponding receptors to reduce the expression and activation of pro-inflammatory composition, govern the transport of immune cells to inflammatory tissues, and restore the integrity of the BBB. Concurrently, FPR1 is essentially related to angiogenesis, cell proliferation and neurogenesis. Thus, treatment with FPRs-modulation may be effective for neurological diseases.

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Section: Formyl Peptide Receptor Action In Neuroinflammationmentioning

confidence: 99%

The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation

Zhu

Ding

et al. 2021

Front. Cell. Neurosci.

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“…Annexin is a well-known calcium-regulated and phospholipid-dependent membrane-binding protein ( Lim and Pervaiz, 2007 ). ANXA1 is a member of the annexin family, which is involved in many important biological processes, such as inflammation, phagocytosis, proliferation, differentiation, and apoptosis ( Monastyrskaya et al, 2009 ; Xia et al, 2020 ). Many studies have shown that ANXA1 is associated with the occurrence, invasion, and metastasis of cancer ( Mussunoor and Murray, 2008 ; Guo et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

ANXA1: An Important Independent Prognostic Factor and Molecular Target in Glioma

et al. 2022

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Objective: The expression, prognosis, and related mechanisms of ANXA1 are investigated in glioma, with the objective to find potential therapeutic molecular targets for glioma.Methods: We analyzed the gene expression of ANXA1 using glioma-related databases, including the Chinese Glioma Genome Atlas (CGGA) database, The Cancer Genome Atlas (TCGA) database, and the Gene Expression Omnibus (GEO) database. Moreover, we collected the sample tissues and corresponding paracancerous tissues of 23 glioma patients and then conducted a Western blot experiment to verify the expression and correlate survival of ANXA1. Moreover, we generated survival ROC curves, performing univariate and multivariate Cox analyses and the construction of the nomogram. Differential expression analysis was conducted by high and low grouping based on the median of the ANXA1 gene expression values. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Set Enrichment Analysis (GSEA) to explore possible mechanisms, and gene co-expression analysis was also performed.Results: The results showed that the ANXA1 expression level was higher in gliomas than in normal tissues, and a high expression level of ANXA1 in gliomas was associated with poorer prognosis. The independent prognosis analysis showed that the ANXA1 gene was an independent prognostic factor of glioma. In the analysis of KEGG and Gene Set Enrichment Analysis (GSEA), it is shown that ANXA1 may play an important role in glioma patients by affecting extracellular matrix (ECM)–receptor interaction and the focal adhesion signal pathway. The core genes, including COL1A1, COL1A2, FN1, ITGA1, and ITGB1, were screened for gene correlation and prognosis analysis. The expression level of the five genes was verified by qPCR in glioma. We concluded that these five core genes and ANXA1 could play a synergistic role in gliomas.Conclusion: The results indicated that a high expression level of ANXA1 leads to worse prognosis and ANXA1 is an independent prognostic factor and a potentially important target for the treatment of gliomas.

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“…SCs are the principal glial cells of peripheral nerves [ 78 ]. They establish myelin sheaths around axons, which contributes to maintaining the integrity of axons and increasing signal transmitting velocity [ 79 ].…”

Section: The Effects Of Exosomes On Schwann Cell Activationmentioning

confidence: 99%

Exosomes as a Promising Therapeutic Strategy for Peripheral Nerve Injury

Ahmad

et al. 2021

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Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives of autologous nerve grafts, and a variety of cells and neurotrophic factors were introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repair capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair. Keywords: Exosome, nerve regeneration, peripheral nerve injury, Schwann cell, axonal regrowth, inflammation, vascular regeneration.

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ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

Cited by 25 publications

References 49 publications

The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation

The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation

ANXA1: An Important Independent Prognostic Factor and Molecular Target in Glioma

Exosomes as a Promising Therapeutic Strategy for Peripheral Nerve Injury

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