Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury
Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission,...
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| Veröffentlicht in: | Glia 2019-01, Vol.67 (1), p.78-90 |
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| creator | Su, Wen‐Feng Wu, Fan Jin, Zi‐Han Gu, Yun Chen, Ying‐Ting Fei, Ying Chen, Hui Wang, Ya‐Xian Xing, Ling‐Yan Zhao, Ya‐Yu Yuan, Ying Tang, Xin Chen, Gang |
| description | Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF‐a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF‐a‐induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.
Main Points
P2X4R is mainly localized in the lysosomes of Schwann cells and the expression of P2X4R in Schwann cells is strikingly upregulated following nerve crush injury.
Overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery as well as accelerates nerve remyelination via BDNF release following nerve injury. |
| doi_str_mv | 10.1002/glia.23527 |
| format | Article |
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Main Points
P2X4R is mainly localized in the lysosomes of Schwann cells and the expression of P2X4R in Schwann cells is strikingly upregulated following nerve crush injury.
Overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery as well as accelerates nerve remyelination via BDNF release following nerve injury.</description><identifier>ISSN: 0894-1491</identifier><identifier>EISSN: 1098-1136</identifier><identifier>DOI: 10.1002/glia.23527</identifier><identifier>PMID: 30306657</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Astrocytes ; Brain-derived neurotrophic factor ; Central nervous system ; Excitability ; Injuries ; Lysosomes ; Microglia ; Motors ; Myelination ; nerve injury ; Nerves ; Nervous system ; P2X4R ; Pain ; Peripheral nervous system ; Peripheral neuropathy ; Protein biosynthesis ; Proteins ; Recovery ; Recovery of function ; Regrowth ; Schwann cell ; Schwann cells ; Secretion ; Synaptic transmission</subject><ispartof>Glia, 2019-01, Vol.67 (1), p.78-90</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5007-70226a9c7f07298df30908b7d4ceb0490b11e1339852bafc0e5db94f7cbd932f3</citedby><cites>FETCH-LOGICAL-c5007-70226a9c7f07298df30908b7d4ceb0490b11e1339852bafc0e5db94f7cbd932f3</cites><orcidid>0000-0003-3669-5687</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fglia.23527$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fglia.23527$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30306657$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Wen‐Feng</creatorcontrib><creatorcontrib>Wu, Fan</creatorcontrib><creatorcontrib>Jin, Zi‐Han</creatorcontrib><creatorcontrib>Gu, Yun</creatorcontrib><creatorcontrib>Chen, Ying‐Ting</creatorcontrib><creatorcontrib>Fei, Ying</creatorcontrib><creatorcontrib>Chen, Hui</creatorcontrib><creatorcontrib>Wang, Ya‐Xian</creatorcontrib><creatorcontrib>Xing, Ling‐Yan</creatorcontrib><creatorcontrib>Zhao, Ya‐Yu</creatorcontrib><creatorcontrib>Yuan, Ying</creatorcontrib><creatorcontrib>Tang, Xin</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><title>Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury</title><title>Glia</title><addtitle>Glia</addtitle><description>Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF‐a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF‐a‐induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.
Main Points
P2X4R is mainly localized in the lysosomes of Schwann cells and the expression of P2X4R in Schwann cells is strikingly upregulated following nerve crush injury.
Overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery as well as accelerates nerve remyelination via BDNF release following nerve injury.</description><subject>Astrocytes</subject><subject>Brain-derived neurotrophic factor</subject><subject>Central nervous system</subject><subject>Excitability</subject><subject>Injuries</subject><subject>Lysosomes</subject><subject>Microglia</subject><subject>Motors</subject><subject>Myelination</subject><subject>nerve injury</subject><subject>Nerves</subject><subject>Nervous system</subject><subject>P2X4R</subject><subject>Pain</subject><subject>Peripheral nervous system</subject><subject>Peripheral neuropathy</subject><subject>Protein biosynthesis</subject><subject>Proteins</subject><subject>Recovery</subject><subject>Recovery of function</subject><subject>Regrowth</subject><subject>Schwann cell</subject><subject>Schwann cells</subject><subject>Secretion</subject><subject>Synaptic transmission</subject><issn>0894-1491</issn><issn>1098-1136</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS1ERYfChgdAltggpJRrO4njZSn0RxpRJEBiFznONWSU2FM7mZIn4XXrzJQuWLCxZZ_vnqujQ8grBqcMgL__2Xf6lIuCyydkxUBVGWOifEpWUKk8Y7lix-R5jBsAlh7yGTkWIKAsC7kif252GPD3NmCMnXfUW_qF_8hpQIPb0QfaOfrV_LrTzlGDfR_pNvjBjxhpOpOuXUsjuujDTO3kzJhcdL_M--Q87_WAw4x95_Qi0l2n6YePny_SmAm4_9J2xEAdhh2mhZspzC_IkdV9xJcP9wn5fvHp2_lVtr65vD4_W2emAJCZBM5LrYy0ILmqWitAQdXINjfYQK6gYQyZEKoqeKOtASzaRuVWmqZVgltxQt4efFOs2wnjWA9dXIJqh36KNWesEkyAlAl98w-68VNIYReqZLKsWKES9e5AmeBjDGjrbegGHeaaQb3UVS911fu6Evz6wXJqBmwf0b_9JIAdgLuux_k_VvXl-vrsYHoPn_ih1w</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Su, Wen‐Feng</creator><creator>Wu, Fan</creator><creator>Jin, Zi‐Han</creator><creator>Gu, Yun</creator><creator>Chen, Ying‐Ting</creator><creator>Fei, Ying</creator><creator>Chen, Hui</creator><creator>Wang, Ya‐Xian</creator><creator>Xing, Ling‐Yan</creator><creator>Zhao, Ya‐Yu</creator><creator>Yuan, Ying</creator><creator>Tang, Xin</creator><creator>Chen, Gang</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3669-5687</orcidid></search><sort><creationdate>201901</creationdate><title>Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury</title><author>Su, Wen‐Feng ; Wu, Fan ; Jin, Zi‐Han ; Gu, Yun ; Chen, Ying‐Ting ; Fei, Ying ; Chen, Hui ; Wang, Ya‐Xian ; Xing, Ling‐Yan ; Zhao, Ya‐Yu ; Yuan, Ying ; Tang, Xin ; Chen, Gang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5007-70226a9c7f07298df30908b7d4ceb0490b11e1339852bafc0e5db94f7cbd932f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Astrocytes</topic><topic>Brain-derived neurotrophic factor</topic><topic>Central nervous system</topic><topic>Excitability</topic><topic>Injuries</topic><topic>Lysosomes</topic><topic>Microglia</topic><topic>Motors</topic><topic>Myelination</topic><topic>nerve injury</topic><topic>Nerves</topic><topic>Nervous system</topic><topic>P2X4R</topic><topic>Pain</topic><topic>Peripheral nervous system</topic><topic>Peripheral neuropathy</topic><topic>Protein biosynthesis</topic><topic>Proteins</topic><topic>Recovery</topic><topic>Recovery of function</topic><topic>Regrowth</topic><topic>Schwann cell</topic><topic>Schwann cells</topic><topic>Secretion</topic><topic>Synaptic transmission</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Wen‐Feng</creatorcontrib><creatorcontrib>Wu, Fan</creatorcontrib><creatorcontrib>Jin, Zi‐Han</creatorcontrib><creatorcontrib>Gu, Yun</creatorcontrib><creatorcontrib>Chen, Ying‐Ting</creatorcontrib><creatorcontrib>Fei, Ying</creatorcontrib><creatorcontrib>Chen, Hui</creatorcontrib><creatorcontrib>Wang, Ya‐Xian</creatorcontrib><creatorcontrib>Xing, Ling‐Yan</creatorcontrib><creatorcontrib>Zhao, Ya‐Yu</creatorcontrib><creatorcontrib>Yuan, Ying</creatorcontrib><creatorcontrib>Tang, Xin</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Glia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Wen‐Feng</au><au>Wu, Fan</au><au>Jin, Zi‐Han</au><au>Gu, Yun</au><au>Chen, Ying‐Ting</au><au>Fei, Ying</au><au>Chen, Hui</au><au>Wang, Ya‐Xian</au><au>Xing, Ling‐Yan</au><au>Zhao, Ya‐Yu</au><au>Yuan, Ying</au><au>Tang, Xin</au><au>Chen, Gang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury</atitle><jtitle>Glia</jtitle><addtitle>Glia</addtitle><date>2019-01</date><risdate>2019</risdate><volume>67</volume><issue>1</issue><spage>78</spage><epage>90</epage><pages>78-90</pages><issn>0894-1491</issn><eissn>1098-1136</eissn><abstract>Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF‐a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF‐a‐induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.
Main Points
P2X4R is mainly localized in the lysosomes of Schwann cells and the expression of P2X4R in Schwann cells is strikingly upregulated following nerve crush injury.
Overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery as well as accelerates nerve remyelination via BDNF release following nerve injury.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30306657</pmid><doi>10.1002/glia.23527</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-3669-5687</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Astrocytes Brain-derived neurotrophic factor Central nervous system Excitability Injuries Lysosomes Microglia Motors Myelination nerve injury Nerves Nervous system P2X4R Pain Peripheral nervous system Peripheral neuropathy Protein biosynthesis Proteins Recovery Recovery of function Regrowth Schwann cell Schwann cells Secretion Synaptic transmission |
| title | Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury |
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