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Article ; Online: Differential expression of circular RNAs in the proximal and distal segments of the sciatic nerve after injury.

Sohn, Eun Jung / Park, Hwan Tae

2019 Volume 31, Issue 1, Page(s) 76–84

Abstract: To investigate the functions of circular RNAs (circRNAs) in axonal regeneration and degeneration after injury, circRNA expression profiles in the injured peripheral nerves were determined using a circRNA-based microarray. The results showed that 281 ... ...

Abstract	To investigate the functions of circular RNAs (circRNAs) in axonal regeneration and degeneration after injury, circRNA expression profiles in the injured peripheral nerves were determined using a circRNA-based microarray. The results showed that 281 upregulated and 261 downregulated circRNAs were found in the proximal stump of the sciatic nerve after injury. In the distal stump after injury, 217 circRNAs were upregulated and 224 circRNAs were downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and gene ontology (GO) analysis of circRNAs after injury were associated with axon regeneration pathways, including thyroid hormone, Ras signaling, endocytosis, and the ErbB signaling pathway, as well as with Schwann cell differentiation and proliferation, including the axon guidance, focal adhesion, Glutamatergic synapse, and MAPK signaling pathway. To verify the microarray results, among the regulated circRNAs, the upregulation of circRNA 012142 in both proximal and distal segments was validated using quantitative PCR analysis. The biological function of the circRNA 012412/microRNA/mRNA network based on GO analysis and KEGG pathway was identified in cell differentiation, phosphorylation, intracellular signaling transduction, and focal adhesion, the Rap1 signaling pathway. Thus, circRNAs after nerve injury may be involved in these biological functions during nerve regeneration and degeneration.
MeSH term(s)	Animals ; Female ; Mice ; Mice, Inbred C57BL ; Nerve Degeneration/genetics ; Nerve Degeneration/physiopathology ; Nerve Regeneration/genetics ; Peripheral Nerve Injuries/genetics ; Peripheral Nerve Injuries/physiopathology ; RNA, Circular/metabolism ; Sciatic Nerve/injuries
Chemical Substances	RNA, Circular
Language	English
Publishing date	2019-11-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000001371
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Article ; Online: Trichinella Infection Ameliorated Vincristine-Induced Neuroinflammation in Mice.

Jo, Young Rae / Park, Hwan Tae / Yu, Hak Sun / Kong, Hyun-Hee

The Korean journal of parasitology

2022 Volume 60, Issue 4, Page(s) 247–254

Abstract: Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by ... ...

Abstract	Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by immune cells such as macrophages can exacerbate allodynia and hyperalgesia, because inhibiting the inflammatory response is a treatment target for VIPN. In this study, we investigated whether Trichinella spiralis, a widely studied helminth for its immunomodulatory abilities, can alleviate VCR-induced allodynia. Von Frey test showed that T. spiralis infection improved mechanical allodynia at 10 days after VCR injection. We further observed whether the difference was due to mitigated axon degeneration, but no significant difference between the groups in axonal degeneration in sciatic nerves and intra-epidermal nerve fibers was found. Conversely, we observed that number of infiltrated macrophages was decreased in the sciatic nerves of the T. spiralis infected mice. Moreover, treatment of T. spiralis excretory-secretory products caused peritoneal macrophages to secrete decreased level of IL-1β. This study suggests that T. spiralis can relieve VCR-induced mechanical allodynia by suppressing neuroinflammation and that application of controllable degree of helminth may prove beneficial for VIPN treatment.
MeSH term(s)	Animals ; Hyperalgesia/chemically induced ; Hyperalgesia/drug therapy ; Mice ; Neuroinflammatory Diseases ; Trichinella ; Trichinella spiralis ; Trichinellosis/drug therapy ; Vincristine/adverse effects
Chemical Substances	Vincristine (5J49Q6B70F)
Language	English
Publishing date	2022-08-24
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	286875-1
ISSN	1738-0006 ; 0023-4001
ISSN (online)	1738-0006
ISSN	0023-4001
DOI	10.3347/kjp.2022.60.4.247
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Article ; Online: Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury.

Sohn, Eun-Jung / Nam, Yun-Kyeong / Park, Hwan-Tae

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: Although microRNAs (miRNAs or miRs) have been studied in the peripheral nervous system, their function in Schwann cells remains elusive. In this study, we performed a microRNA array analysis of cyclic adenosine monophosphate (cAMP)-induced differentiated ...

Abstract	Although microRNAs (miRNAs or miRs) have been studied in the peripheral nervous system, their function in Schwann cells remains elusive. In this study, we performed a microRNA array analysis of cyclic adenosine monophosphate (cAMP)-induced differentiated primary Schwann cells.
MeSH term(s)	Animals ; Cells, Cultured ; Down-Regulation/physiology ; Female ; Mice ; Mice, Inbred C57BL ; MicroRNAs/metabolism ; Myelin Sheath/metabolism ; Peripheral Nerve Injuries/metabolism ; Phenotype ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X4/metabolism ; Schwann Cells/metabolism ; Signal Transduction/physiology ; Up-Regulation/physiology
Chemical Substances	MicroRNAs ; P2rx4 protein, mouse ; Receptors, Purinergic P2X4 ; microRNA 363, mouse
Language	English
Publishing date	2021-10-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222111601
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Article ; Online: Regulation of the V-ATPase subunit ATP6V0D2 and its role in demyelination after peripheral nerve injury.

Shin, Yoon Kyung / Jo, Young Rae / Lee, Seoung Hoon / Park, Hwan Tae / Shin, Jung Eun

Biochemical and biophysical research communications

2023 Volume 646, Page(s) 1–7

Abstract: After peripheral nerve injury, demyelinating Schwann cells discharge myelin debris and macrophages execute myelin degradation, leading to demyelination of degenerating axons, which is essential for efficient nerve regeneration. In this study, we show ... ...

Abstract	After peripheral nerve injury, demyelinating Schwann cells discharge myelin debris and macrophages execute myelin degradation, leading to demyelination of degenerating axons, which is essential for efficient nerve regeneration. In this study, we show that vacuolar-type proton ATPase subunit d2 (Atp6v0d2) is among the most highly upregulated genes in degenerating mouse sciatic nerves after nerve injury using microarray analysis. ATP6V0D2 is mostly expressed in macrophages of injured nerves. Atp6v0d2 knockout mice display delayed peripheral nerve demyelination and significantly attenuated myelin lipid digestion after nerve injury. However, macrophage recruitment and Schwann cell dedifferentiation are unaffected by loss of Atp6v0d2 expression. Taken together, these data demonstrate that ATP6V0D2 in macrophages is specifically required for demyelination during Wallerian degeneration.
MeSH term(s)	Mice ; Animals ; Peripheral Nerve Injuries/metabolism ; Adenosine Triphosphatases/metabolism ; Myelin Sheath/metabolism ; Schwann Cells/metabolism ; Wallerian Degeneration ; Sciatic Nerve/metabolism ; Mice, Knockout ; Demyelinating Diseases/metabolism ; Nerve Regeneration ; Vacuolar Proton-Translocating ATPases/genetics ; Vacuolar Proton-Translocating ATPases/metabolism
Chemical Substances	Adenosine Triphosphatases (EC 3.6.1.-) ; Atp6v0d2 protein, mouse (EC 3.6.1.-) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-)
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.01.039
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Article ; Online: MicroRNA Mediated Regulation of Schwann Cell Migration and Proliferation in Peripheral Nerve Injury.

Sohn, Eun Jung / Park, Hwan Tae

BioMed research international

2018 Volume 2018, Page(s) 8198365

Abstract: Schwann cells (SCs) contribute to nerve repair following injury; however, the underlying molecular mechanism is poorly understood. MicroRNAs (miRNAs), which are short noncoding RNAs, have been shown to play a role in neuronal disease. In this work, we ... ...

Abstract	Schwann cells (SCs) contribute to nerve repair following injury; however, the underlying molecular mechanism is poorly understood. MicroRNAs (miRNAs), which are short noncoding RNAs, have been shown to play a role in neuronal disease. In this work, we show that miRNAs regulate the peripheral nerve system by modulating the migration and proliferation of SCs. Thus, miRNAs expressed in peripheral nerves may provide a potential therapeutic target for peripheral nerve injury or repair.
MeSH term(s)	Animals ; Cell Movement/genetics ; Cell Movement/physiology ; Cell Proliferation/genetics ; Cell Proliferation/physiology ; Humans ; MicroRNAs/genetics ; Peripheral Nerve Injuries/genetics ; Peripheral Nerve Injuries/pathology ; Schwann Cells/pathology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2018-04-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2018/8198365
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Article ; Online: Exosomes derived from differentiated Schwann cells inhibit Schwann cell migration via microRNAs.

Sohn, Eun Jung / Park, Hwan Tae / Shin, Yoon Kyung

Neuroreport

2020 Volume 31, Issue 7, Page(s) 515–522

Abstract: Exosomes derived from Schwann cells have been known to have a variety of functions in the development and repair of the peripheral nervous system, and cyclic AMP (cAMP) is a key inducer of Schwann cell differentiation. In the present study, we aimed to ... ...

Abstract	Exosomes derived from Schwann cells have been known to have a variety of functions in the development and repair of the peripheral nervous system, and cyclic AMP (cAMP) is a key inducer of Schwann cell differentiation. In the present study, we aimed to study the effect of exosomes derived from differentiated Schwann cells on the expression of microRNAs (miRNAs). To show that miRNAs were altered from exosomes derived from Schwann cells, we conducted next-generation sequencing (NGS) arrays with exosomes derived from cAMP-induced differentiated Schwann cells and control. NGS arrays revealed that 22 miRNAs, 33 small nucleolar RNAs, one antisense RNA, and two mRNAs were upregulated, while 37 mRNAs, one tRNA, and 35 antisense RNAs were downregulated. We also confirmed that miRNA211 and miR92a-3p were upregulated, while the expression levels of hypoxia-inducible factor, rat cyclin-dependent kinase 2, and rat platelet-derived growth factor C were reduced in exosomes derived from cAMP-induced differentiated Schwann cells. Venn diagrams were used to identify overlapping miRNA targets from highly expressed miRNAs (miR211-5p, miR211-3p, and miR92a-3p). The pathways identified via Kyoto Encyclopedia of Genes and Genomes analysis of the target genes are associated with nerve regeneration and Schwann cell proliferation such as the tumor necrosis factor signaling pathway, dopaminergic synapse, and neurotrophin signaling, and cAMP-dependent signaling pathways. Additionally, we observed that exosomes derived from differentiated Schwann cells suppressed Schwann cell migration, while control exosomes obtained from undifferentiated Schwann cells did not. Together, the results suggested that exosomes released from differentiated Schwann cells regulated Schwann cell migration through changes in miRNA expression.
MeSH term(s)	Animals ; Cell Movement ; Cells, Cultured ; Exosomes/metabolism ; Gene Expression ; High-Throughput Nucleotide Sequencing ; MicroRNAs/metabolism ; Rats ; Schwann Cells/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2020-03-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000001435
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Zs.A 3118: Show issues

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Article: Natural agents mediated autophagic signal networks in cancer.

Sohn, Eun Jung / Park, Hwan Tae

Cancer cell international

2017 Volume 17, Page(s) 110

Abstract: Recent studies suggested that natural compounds are important in finding targets for cancer treatments. Autophagy ("self-eating") plays important roles in multiple diseases and acts as a tumor suppressor in cancer. Here, we examined the molecular ... ...

Abstract	Recent studies suggested that natural compounds are important in finding targets for cancer treatments. Autophagy ("self-eating") plays important roles in multiple diseases and acts as a tumor suppressor in cancer. Here, we examined the molecular mechanism by which natural agents regulate autophagic signals. Understanding the relationship between natural agents and cellular autophagy may provide more information for cancer diagnosis and chemoprevention.
Language	English
Publishing date	2017-11-28
Publishing country	England
Document type	Journal Article ; Review
ISSN	1475-2867
ISSN	1475-2867
DOI	10.1186/s12935-017-0486-7
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Article ; Online: Wallerian demyelination: chronicle of a cellular cataclysm.

Tricaud, Nicolas / Park, Hwan Tae

Cellular and molecular life sciences : CMLS

2017 Volume 74, Issue 22, Page(s) 4049–4057

Abstract: Wallerian demyelination is characteristic of peripheral nerve degeneration after traumatic injury. After axonal degeneration, the myelinated Schwann cell undergoes a stereotypical cellular program that results in the disintegration of the myelin sheath, ... ...

Abstract	Wallerian demyelination is characteristic of peripheral nerve degeneration after traumatic injury. After axonal degeneration, the myelinated Schwann cell undergoes a stereotypical cellular program that results in the disintegration of the myelin sheath, a process termed demyelination. In this review, we chronologically describe this program starting from the late and visible features of myelin destruction and going backward to the initial molecular steps that trigger the nuclear reprogramming few hours after injury. Wallerian demyelination is a wonderful model for myelin degeneration occurring in the diverse forms of demyelinating peripheral neuropathies that plague human beings.
MeSH term(s)	Axons/physiology ; Cell Dedifferentiation ; Cellular Reprogramming ; Humans ; MAP Kinase Signaling System ; Mitochondria/metabolism ; Myelin Sheath/metabolism ; Schwann Cells/metabolism ; Wallerian Degeneration/metabolism ; Wallerian Degeneration/pathology
Language	English
Publishing date	2017-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-017-2565-2
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Article ; Online: Downregulation MIWI-piRNA regulates the migration of Schwann cells in peripheral nerve injury.

Sohn, Eun Jung / Jo, Young Rae / Park, Hwan Tae

Biochemical and biophysical research communications

2019 Volume 519, Issue 3, Page(s) 605–612

Abstract: Although MIWI (PIWI in humans) regulates spermatogenesis and translation machinery, its role in peripheral nerve injury is poorly understood. In this study, we characterized the expression profiles of MIWI after sciatic nerve injury. The results revealed ...

Abstract	Although MIWI (PIWI in humans) regulates spermatogenesis and translation machinery, its role in peripheral nerve injury is poorly understood. In this study, we characterized the expression profiles of MIWI after sciatic nerve injury. The results revealed that MIWI was downregulated after sciatic nerve injury. MIWI was colocalized with S100 (a Schwan cell marker), and TOM20 (a mitochondrial marker) on uncut nerves, while some MIWI was also colocalized with myelin protein zero (a myelin marker) on injured nerves. Immunofluorescence revealed that some MIWI was colocalized with SOX10 in the nuclear compartment following nerve injury. MIWI depletion by MIWI siRNA resulted in the reduction of EGR2. To characterize the expression of PIWI interacting RNA (piRNA) during sciatic nerve injury, microarray-based piRNA was conducted. The results revealed that 3447 piRNAs were upregulated, while 4117 piRNAs were downregulated after nerve transection. Interestingly, piR 009614 downregulated the mRNA level of MBP and enhanced the migration of RT-4 Schwann cells. Together, our results suggest that the MIWI-piRNA complex may play a role in Schwann cell responses to nerve injury.
MeSH term(s)	Animals ; Argonaute Proteins/metabolism ; Cell Movement ; Cells, Cultured ; Down-Regulation ; Mice ; Mice, Inbred C57BL ; Peripheral Nerve Injuries/metabolism ; Peripheral Nerve Injuries/pathology ; RNA, Small Interfering/metabolism ; Schwann Cells/metabolism ; Schwann Cells/pathology
Chemical Substances	Argonaute Proteins ; Piwil1 protein, mouse ; RNA, Small Interfering
Language	English
Publishing date	2019-09-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2019.09.008
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Article ; Online: Scaffolding protein Gab2 is involved in postnatal development and lipopolysaccharide-induced activation of microglia in the mouse brain.

Byeon, Jae Woong / Jo, Young Rae / Shin, Yoon Kyung / Park, Hwan Tae / Park, Hyun-Seok

Biochemical and biophysical research communications

2021 Volume 567, Page(s) 112–117

Abstract: Grb2-associated-binding protein-2 (Gab2) is a member of the Gab/DOS family and functions as an adapter protein downstream of several growth factor signaling pathways. Gab2 is considered an Alzheimer's disease susceptibility gene. However, the role of ... ...

Abstract	Grb2-associated-binding protein-2 (Gab2) is a member of the Gab/DOS family and functions as an adapter protein downstream of several growth factor signaling pathways. Gab2 is considered an Alzheimer's disease susceptibility gene. However, the role of Gab2 in the brain is still largely unknown. Herein, we report that Gab2 is involved in the postnatal development of microglia in mice. The Gab2 expression in the brain was detected at postnatal day 1 (P1) and increased until P14 but decreased thereafter. The tyrosine phosphorylation of Gab2 (pGab2) was also detected at P1 and increased until P14. Next, we focused on microglial development in Gab2 knockout and heterozygous mice. Although differences were not detected in the cytoplasmic area of Iba1-labeled microglia between Gab2(±) and Gab2(-/-) mice, the analysis of CD68 and cathepsin D (indicators of microglial lysosomal activation) immunolabeling within Iba1+ cells revealed significant underdevelopment of microglial lysosomes in Gab2(-/-) mice at P60. In addition to the developmental abnormality of microglia in Gab2(-/-) mice, lipopolysaccharide-induced lysosomal activation was selectively suppressed in Gab2(-/-) mice compared to that in Gab2(±) mice. Our findings suggest that Gab2 is involved not only in postnatal development but also in lysosomal activation of microglia, therefore Gab2 dysfunction in microglia might potentially contribute to the development of neurodegenerative diseases.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Brain/growth & development ; Brain/metabolism ; Cell Line ; Gene Expression Regulation, Developmental ; Lipopolysaccharides/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Gab2 protein, mouse ; Lipopolysaccharides
Language	English
Publishing date	2021-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2021.06.028
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