Hepatocyte Growth Factor (HGF) Promotes Peripheral Nerve Regeneration by Activating Repair Schwann Cells

Ko, Kyeong Ryang; Lee, Jung-Hun; Lee, Deokho; Nho, Boram; Kim, Sun‐Young

doi:10.1038/s41598-018-26704-x

Cited by 78 publications

(83 citation statements)

References 48 publications

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“…HGF discovered in 1991, was demonstrated to play an important role in cell survival, tissue regeneration, and inflammation regulation in various injury and disease (Kitamura et al, 2011; Nakamura et al, 2011; Jeong et al, 2012; Ko et al, 2018; Li et al, 2018; Pang et al, 2018). It reduced the expression level of IL-6 , TNF-α , and intercellular adhesion molecule-1 ( ICAM-1 ) by regulating NF-kB signaling in pulmonary artery hypertension rat (Pang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Conditioned Medium of Human Menstrual Blood-Derived Endometrial Stem Cells Protects Against MPP+-Induced Cytotoxicity in vitro

Han

Yahaya

et al. 2019

Front. Mol. Neurosci.

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Mesenchymal stem cells (MSCs) showed the potential to treat Parkinson’s disease (PD). However, it is unknown whether the conditioned medium of human menstrual blood-derived endometrial stem cells (MenSCs-CM) has the function to alleviate syndromes of PD. In this study, human neuroblastoma SH-SY5Y cells were exposed to neurotoxicant 1-methyl-4-phenylpyridinium (MPP + ) for inducing a range of response characteristics of PD. After culturing this cell model with 24 h/48 h collected MenSCs-CM for different days, cell viability, pro-inflammation cytokines, mitochondrial membrane potential (ΔΨm), oxidative stress, and cell apoptosis were detected. Finally, protein assay was performed to detect 12 kinds of neurotrophic factors inside MenSCs-CM. Our results showed that MPP + caused SH-SY5Y cell viability reduction as an increasing dose and time dependent manner. MPP + treatment resulted in inflammation, mitochondrial dysfunction, reactive oxygen species (ROS) production accumulation, and apoptosis of SH-SY5Y at its IC50 concentration. Forty-eight hours-collected MenSCs-CM and culturing with the MPP + -treated SH-SY5Y for 2 days are the optimized condition to increase cell viability. Besides, MenSCs-CM was efficacious against MPP + induced inflammation, ΔΨm loss, ROS generation, and it could significantly decrease cells numbers in late apoptosis stage. What’s more, protein assay showed that MenSCs-CM contained various neuroprotective factors. Our study provided the first evidence that MenSCs-CM has a protective effect on MPP + -induced cytotoxicity in various aspects, and firstly showed that MenSCs can release at least 12 kinds of neurotrophic factors to medium, which may contribute to the protective function of MenSCs-CM to treat PD. This research enlightening that MenSCs-CM is beneficial in the therapy for PD and probably also for other neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Conditioned Medium of Human Menstrual Blood-Derived Endometrial Stem Cells Protects Against MPP+-Induced Cytotoxicity in vitro

Han

Yahaya

et al. 2019

Front. Mol. Neurosci.

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“…Decreased myelin stability and reduced internodal length are observed without changes in myelin thickness, whereas in unmyelinated fibers Remak bundle formation is disrupted (Cervellini et al, ). In contrast, another recent study demonstrates that ERK activation induced by hepatocyte growth factor improves remyelination through enhanced Schwann cell migration after a sciatic nerve crush (Ko et al, ). Taken together, these results emphasize the importance of the strength, duration, and location of ERK activation during PNS regeneration.…”

Section: Introductionmentioning

confidence: 95%

Promotion of Peripheral Nerve Regeneration by Stimulation of the Extracellular Signal‐Regulated Kinase (ERK) Pathway

Hausott

Klimaschewski

2019

The Anatomical Record

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Peripherally projecting neurons undergo significant morphological changes during development and regeneration. This neuroplasticity is controlled by growth factors, which bind specific membrane bound kinase receptors that in turn activate two major intracellular signal transduction cascades. Besides the PI3 kinase/AKT pathway, activated extracellular signal‐regulated kinase (ERK) plays a key role in regulating the mode and speed of peripheral axon outgrowth in the adult stage. Cell culture studies and animal models revealed that ERK signaling is mainly involved in elongative axon growth in vitro and long‐distance nerve regeneration in vivo. Here, we review ERK dependent morphological plasticity in adult peripheral neurons and evaluate the therapeutic potential of interfering with regulators of ERK signaling to promote nerve regeneration. Anat Rec, 302:1261–1267, 2019. © 2019 Wiley Periodicals, Inc.

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“…The regeneration process of the injured sciatic nerve has been well documented in human and animal experiments (Ko et al, 2018;Wanner et al, 2017). Specifically, Schwann cell proliferation is generated at the early stage of the regeneration and proliferating cells migrate toward the distal region to the injury site by releasing neurotrophic factors.…”

Section: Introductionmentioning

confidence: 99%

Treadmill exercise activates ATF3 and ERK1/2 downstream molecules to facilitate axonal regrowth after sciatic nerve injury

2020

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The purpose of this study was to investigate the effect of treadmill exercise on activating transcription factors such as activating transcription factor 3 (ATF3) and extracellular signal-regulated kinase (ERK1/2) signaling pathway to facilitate axonal regrowth after sciatic nerve injury (SNI). The experimental rats divided into the normal control (n = 10), sedentary groups for 7 (n= 10) and 14 days (n= 10) post crush, exercise group for 7 (n= 10) and 14 days (n= 10) post crush (dpc). The rats in exercise groups run on treadmill device at a speed of 8 m/min for 20 min once a day according to exercise duration. In order to evaluate specific regeneration markers and axonal elongation in injured sciatic nerve, we applied immunofluorescence staining and western blot techniques. Treadmill exercise further increased growth-associated protein (GAP-43) expression and axonal regrowth at 7 and 14 dpc than those in sedentary group. Among mitogen-activated protein kinase downstream molecules, phospho-ERK1/2 (p-ERK1/2) was enhanced by treadmill exercise at only 7 dpc and decreased to basal level 14 days later. But c-Jun N-terminal kinase, c-Jun, and phospho-cyclic adenosine monophosphate response element-binding protein showed a tendency to increase continuously until 14 dpc by exercise. ATF3 expression in exercise group was upregulated at both 7 and 14 dpc compared to the sedentary group. These results indicate that treadmill exercise had beneficial effect on expression of regeneration-related proteins after SNI, suggesting that exercise might be one of various therapeutic strategies for sciatic nerve regeneration.

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Hepatocyte Growth Factor (HGF) Promotes Peripheral Nerve Regeneration by Activating Repair Schwann Cells

Cited by 78 publications

References 48 publications

Conditioned Medium of Human Menstrual Blood-Derived Endometrial Stem Cells Protects Against MPP+-Induced Cytotoxicity in vitro

Conditioned Medium of Human Menstrual Blood-Derived Endometrial Stem Cells Protects Against MPP+-Induced Cytotoxicity in vitro

Promotion of Peripheral Nerve Regeneration by Stimulation of the Extracellular Signal‐Regulated Kinase (ERK) Pathway

Treadmill exercise activates ATF3 and ERK1/2 downstream molecules to facilitate axonal regrowth after sciatic nerve injury

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