Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury

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. <i>KEGG</i>...

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Autores principales:	Eun-Jung Sohn, Yun-Kyeong Nam, Hwan-Tae Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microRNA Wallerian degeneration Schwann cells miRNA 363-5p Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3d2c4851dfd644cbba215711a61e2ec6
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spelling	oai:doaj.org-article:3d2c4851dfd644cbba215711a61e2ec62021-11-11T17:04:43ZInvolvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury10.3390/ijms2221116011422-00671661-6596https://doaj.org/article/3d2c4851dfd644cbba215711a61e2ec62021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11601https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Although 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. <i>KEGG</i> pathway enrichment analysis of the target genes showed that upregulated miRNAs (mR212-5p, miR335, miR20b-5p, miR146b-3p, and miR363-5p) were related to the calcium signaling pathway, regulation of actin cytoskeleton, retrograde endocannabinoid signaling, and central carbon metabolism in cancer. Several key factors, such as purinergic receptors (P2X), guanine nucleotide-binding protein G(olf) subunit alpha (GNAL), P2RX5, P2RX3, platelet-derived growth factor receptor alpha (PDGFRA), and inositol 1,4,5-trisphosphate receptor type 2 (ITPR2; calcium signaling pathway) are potential targets of miRNAs regulating cAMP. Our analysis revealed that miRNAs were differentially expressed in cAMP-treated Schwann cells; miRNA363-5p was upregulated and directly targeted the P2X purinoceptor 4 (P2RX4)-UTR, reducing the luciferase activity of P2RX4. The expression of miRNA363-5p was inhibited and the expression of P2RX4 was upregulated in sciatic nerve injury. In contrast, miRNA363-5p expression was upregulated and P2RX4 expression was downregulated during postnatal development. Of note, a P2RX4 antagonist counteracted myelin degradation after nerve injury and increased pERK and c-Jun expression. Interestingly, a P2RX4 antagonist increased the levels of miRNA363-5p. This study suggests that a double-negative feedback loop between miRNA363-5p and P2RX4 contributes to the dedifferentiation and migration of Schwann cells after nerve injury.Eun-Jung SohnYun-Kyeong NamHwan-Tae ParkMDPI AGarticlemicroRNAWallerian degenerationSchwann cellsmiRNA 363-5pBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11601, p 11601 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNA Wallerian degeneration Schwann cells miRNA 363-5p Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	microRNA Wallerian degeneration Schwann cells miRNA 363-5p Biology (General) QH301-705.5 Chemistry QD1-999 Eun-Jung Sohn Yun-Kyeong Nam Hwan-Tae Park Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury
description	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. <i>KEGG</i> pathway enrichment analysis of the target genes showed that upregulated miRNAs (mR212-5p, miR335, miR20b-5p, miR146b-3p, and miR363-5p) were related to the calcium signaling pathway, regulation of actin cytoskeleton, retrograde endocannabinoid signaling, and central carbon metabolism in cancer. Several key factors, such as purinergic receptors (P2X), guanine nucleotide-binding protein G(olf) subunit alpha (GNAL), P2RX5, P2RX3, platelet-derived growth factor receptor alpha (PDGFRA), and inositol 1,4,5-trisphosphate receptor type 2 (ITPR2; calcium signaling pathway) are potential targets of miRNAs regulating cAMP. Our analysis revealed that miRNAs were differentially expressed in cAMP-treated Schwann cells; miRNA363-5p was upregulated and directly targeted the P2X purinoceptor 4 (P2RX4)-UTR, reducing the luciferase activity of P2RX4. The expression of miRNA363-5p was inhibited and the expression of P2RX4 was upregulated in sciatic nerve injury. In contrast, miRNA363-5p expression was upregulated and P2RX4 expression was downregulated during postnatal development. Of note, a P2RX4 antagonist counteracted myelin degradation after nerve injury and increased pERK and c-Jun expression. Interestingly, a P2RX4 antagonist increased the levels of miRNA363-5p. This study suggests that a double-negative feedback loop between miRNA363-5p and P2RX4 contributes to the dedifferentiation and migration of Schwann cells after nerve injury.
format	article
author	Eun-Jung Sohn Yun-Kyeong Nam Hwan-Tae Park
author_facet	Eun-Jung Sohn Yun-Kyeong Nam Hwan-Tae Park
author_sort	Eun-Jung Sohn
title	Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury
title_short	Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury
title_full	Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury
title_fullStr	Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury
title_full_unstemmed	Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury
title_sort	involvement of the mir-363-5p/p2rx4 axis in regulating schwann cell phenotype after nerve injury
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3d2c4851dfd644cbba215711a61e2ec6
work_keys_str_mv	AT eunjungsohn involvementofthemir3635pp2rx4axisinregulatingschwanncellphenotypeafternerveinjury AT yunkyeongnam involvementofthemir3635pp2rx4axisinregulatingschwanncellphenotypeafternerveinjury AT hwantaepark involvementofthemir3635pp2rx4axisinregulatingschwanncellphenotypeafternerveinjury
_version_	1718432171890311168

Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury

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