FGF9 alters the Wallerian degeneration process by inhibiting Schwann cell transformation and accelerating macrophage infiltration

Lv, Wenjing; Deng, Binbin; Duan, Weisong; Li, Yi; Song, Xueqin; Ji, Yingxiao; Li, Zhongyao; Liu, Yakun; Wang, Xiaoxiao; Li, Chunyan

doi:10.1016/j.brainresbull.2019.06.011

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…Concurrently, the presentation of CCL2 was significantly lower following MiDs treatment compared with tFNAs or miR‐22 treatment. The expression of neurotrophic factors fiber growth factor 9 (FGF‐9), which is beneficial for SCs maturation and myelination, [ 45 ] was significantly upregulated after MiDs treatment (Figure S9b, Supporting Information). Since nerve repair follows a particular temporal sequence in terms of gene expression, structure, and function, [ 10 ] this result indicates that MiDs might shorten the time required for SCs to respond to injury.…”

Section: Resultsmentioning

confidence: 99%

Modulation of the Crosstalk between Schwann Cells and Macrophages for Nerve Regeneration: A Therapeutic Strategy Based on a Multifunctional Tetrahedral Framework Nucleic Acids System

Yao

Wang

et al. 2022

Advanced Materials

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Peripheral nerve injury (PNI) is currently recognized as one of the most significant public health issues and affects the general well‐being of millions of individuals worldwide. Despite advances in nerve tissue engineering, nerve repair still cannot guarantee complete functional recovery. In the present study, an innovative approach is adopted to establish a multifunctional tetrahedral framework nucleic acids (tFNAs) system, denoted as MiDs, which can integrate the powerful programmability, permeability, and structural stability of tFNAs, with the nerve regeneration potential of microRNA‐22 to enhance the communication between Schwann cells (SCs) and macrophages for more effective functional rehabilitation of peripheral nerves. Relevant results demonstrate that MiDs can amplify the ability of SCs to recruit macrophages and facilitate their polarization into the pro‐healing M2 phenotype to reconstruct the post‐injury microenvironment. Furthermore, MiDs can initiate the adaptive intracellular reprogramming of SCs within a short period to further promote axon regeneration and remyelination. MiDs represent a new possibility for enhancing nerve repair and may have critical clinical applications in the future.

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Section: Resultsmentioning

confidence: 99%

Modulation of the Crosstalk between Schwann Cells and Macrophages for Nerve Regeneration: A Therapeutic Strategy Based on a Multifunctional Tetrahedral Framework Nucleic Acids System

Yao

Wang

et al. 2022

Advanced Materials

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“…Additionally, the phenotype of the macrophages also undergoes changes. There is an obvious increase in pro‐inflammatory M1 macrophages 1–2 days after injury and polarization toward the pro‐regenerative and anti‐inflammatory M2 macrophages 3–4 days after injury, which reduces the local inflammatory response and promotes nerve regeneration (Lv et al, 2019; Peluffo et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Electrical stimulation accelerates Wallerian degeneration and promotes nerve regeneration after sciatic nerve injury

Zhang

et al. 2022

Glia

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Following peripheral nerve injury (PNI), Wallerian degeneration (WD) in the distal stump can generate a microenvironment favorable for nerve regeneration. Brief low‐frequency electrical stimulation (ES) is an effective treatment for PNI, but the mechanism underlying its effect on WD remains unclear. Therefore, we hypothesized that ES could enhance nerve regeneration by accelerating WD. To verify this hypothesis, we used a rat model of sciatic nerve transection and provided ES at the distal stump of the injured nerve. The injured nerve was then evaluated after 1, 4, 7, 14 and 21 days post injury (dpi). The results showed that ES significantly promoted the degeneration and clearance of axons and myelin, and the dedifferentiation of Schwann cells. It upregulated the expression of BDNF and NGF and increased the number of monocytes and macrophages. Through transcriptome sequencing, we systematically investigated the effect of ES on the molecular processes involved in WD at 4 dpi. Evaluation of nerves bridged using silicone tubing after transection showed that ES accelerated early axonal and vascular regeneration while delaying gastrocnemius atrophy. These results demonstrate that ES promotes nerve regeneration by accelerating WD and upregulating the expression of neurotrophic factors.

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“…Deficiency of FGF9 results in a deteriorated infiltration of macrophages and consequently delayed debris clearance. Moreover, decreased expression of the cytokines monocyte chemotactic protein 1 (Mcp1), tumor necrosis factor a (Tnfa), and interleukin 1b (Il-1b) was detected due to the absence of FGF9 [ 70 ]. Neurotrimin (NTM), a member of the neural cell adhesion molecules (NCAM) family, promotes SC migration and plays a crucial role in axon guidance during nerve regeneration [ 71 ].…”

Section: Resultsmentioning

confidence: 99%

“…Besides the use in acute nerve injuries, the field of application is widespread due to the possibility of a two-way modulation of certain processes. In particular, an enhanced inflammation is beneficial during Wallerian degeneration [ 70 ]. The inhibition of miR-182 leads to higher levels of the proinflammatory FGF9 and thus a facilitated invasion of immune cells and more rapid clearance of debris [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration—A Systemic Review

Borger

Stadlmayr

Haertinger

et al. 2022

IJMS

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A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.

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FGF9 alters the Wallerian degeneration process by inhibiting Schwann cell transformation and accelerating macrophage infiltration

Cited by 10 publications

References 38 publications

Modulation of the Crosstalk between Schwann Cells and Macrophages for Nerve Regeneration: A Therapeutic Strategy Based on a Multifunctional Tetrahedral Framework Nucleic Acids System

Modulation of the Crosstalk between Schwann Cells and Macrophages for Nerve Regeneration: A Therapeutic Strategy Based on a Multifunctional Tetrahedral Framework Nucleic Acids System

Electrical stimulation accelerates Wallerian degeneration and promotes nerve regeneration after sciatic nerve injury

How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration—A Systemic Review

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