Silencing of miR20a Is Crucial for Ngn1-Mediated Neuroprotection in Injured Spinal Cord
MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several...
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| Veröffentlicht in: | Human gene therapy 2012-05, Vol.23 (5), p.508-520 |
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| creator | Jee, Min Ki Jung, Jin Sun Im, Young Bin Jung, Sung Jun Kang, Soo Kyung |
| description | MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI). In the current study, we focused on miR20a, which causes continuing motor neuron degeneration when overexpressed in SCI lesions. Blocking miR20a in SCI animals led to neural cell survival and eventual neurogenesis with rescued expression of the key target gene, neurogenin 1 (Ngn1). Infusion of siNgn1 resulted in functional deficit in the hindlimbs caused by aggressive secondary injury and actively enhanced the inflammation involved in secondary injury progression. The events involving miR20a underlie motor neuron and myelin destruction and pathophysiology and ultimately block regeneration in injured spinal cords. Inhibition of miR20a expression effectively induced definitive motor neuron survival and neurogenesis, and SCI animals showed improved functional deficit. In this study, we showed that abnormal expression of miR20a induces secondary injury, which suggests that miR20a could be a potential target for therapeutic intervention following SCI. |
| doi_str_mv | 10.1089/hum.2011.121 |
| format | Article |
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Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI). In the current study, we focused on miR20a, which causes continuing motor neuron degeneration when overexpressed in SCI lesions. Blocking miR20a in SCI animals led to neural cell survival and eventual neurogenesis with rescued expression of the key target gene, neurogenin 1 (Ngn1). Infusion of siNgn1 resulted in functional deficit in the hindlimbs caused by aggressive secondary injury and actively enhanced the inflammation involved in secondary injury progression. The events involving miR20a underlie motor neuron and myelin destruction and pathophysiology and ultimately block regeneration in injured spinal cords. Inhibition of miR20a expression effectively induced definitive motor neuron survival and neurogenesis, and SCI animals showed improved functional deficit. In this study, we showed that abnormal expression of miR20a induces secondary injury, which suggests that miR20a could be a potential target for therapeutic intervention following SCI.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2011.121</identifier><identifier>PMID: 22182208</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Basic Helix-Loop-Helix Transcription Factors - administration & dosage ; Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biological and medical sciences ; Biotechnology ; Cell survival ; Cell Survival - genetics ; Degeneration ; Disease Models, Animal ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - genetics ; Gene therapy ; Health. Pharmaceutical industry ; Hindlimb - pathology ; Humans ; Industrial applications and implications. Economical aspects ; Inflammation ; Medical sciences ; Mice ; MicroRNAs - antagonists & inhibitors ; MicroRNAs - genetics ; miRNA ; Motor neurons ; Motor Neurons - metabolism ; Motor Neurons - pathology ; Myelin ; Myelin Sheath - pathology ; Nerve Tissue Proteins - administration & dosage ; Nerve Tissue Proteins - antagonists & inhibitors ; Nerve Tissue Proteins - metabolism ; Neurogenesis ; neurogenin 1 ; Neuroprotection ; Regeneration ; RNA Interference ; Spinal Cord - metabolism ; Spinal Cord - pathology ; Spinal Cord Injuries - metabolism ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - therapy ; Spinal cord injury ; Therapeutic applications ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Human gene therapy, 2012-05, Vol.23 (5), p.508-520</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-d34901a8d6514b7d49ff6529f0d760ba9ae7f4036d0fd77588abaa02767cc1303</citedby><cites>FETCH-LOGICAL-c354t-d34901a8d6514b7d49ff6529f0d760ba9ae7f4036d0fd77588abaa02767cc1303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26259053$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22182208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jee, Min Ki</creatorcontrib><creatorcontrib>Jung, Jin Sun</creatorcontrib><creatorcontrib>Im, Young Bin</creatorcontrib><creatorcontrib>Jung, Sung Jun</creatorcontrib><creatorcontrib>Kang, Soo Kyung</creatorcontrib><title>Silencing of miR20a Is Crucial for Ngn1-Mediated Neuroprotection in Injured Spinal Cord</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI). In the current study, we focused on miR20a, which causes continuing motor neuron degeneration when overexpressed in SCI lesions. Blocking miR20a in SCI animals led to neural cell survival and eventual neurogenesis with rescued expression of the key target gene, neurogenin 1 (Ngn1). Infusion of siNgn1 resulted in functional deficit in the hindlimbs caused by aggressive secondary injury and actively enhanced the inflammation involved in secondary injury progression. The events involving miR20a underlie motor neuron and myelin destruction and pathophysiology and ultimately block regeneration in injured spinal cords. Inhibition of miR20a expression effectively induced definitive motor neuron survival and neurogenesis, and SCI animals showed improved functional deficit. In this study, we showed that abnormal expression of miR20a induces secondary injury, which suggests that miR20a could be a potential target for therapeutic intervention following SCI.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Basic Helix-Loop-Helix Transcription Factors - administration & dosage</subject><subject>Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cell survival</subject><subject>Cell Survival - genetics</subject><subject>Degeneration</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation - genetics</subject><subject>Gene therapy</subject><subject>Health. Pharmaceutical industry</subject><subject>Hindlimb - pathology</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Inflammation</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>MicroRNAs - antagonists & inhibitors</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Motor neurons</subject><subject>Motor Neurons - metabolism</subject><subject>Motor Neurons - pathology</subject><subject>Myelin</subject><subject>Myelin Sheath - pathology</subject><subject>Nerve Tissue Proteins - administration & dosage</subject><subject>Nerve Tissue Proteins - antagonists & inhibitors</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurogenesis</subject><subject>neurogenin 1</subject><subject>Neuroprotection</subject><subject>Regeneration</subject><subject>RNA Interference</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - pathology</subject><subject>Spinal Cord Injuries - metabolism</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - therapy</subject><subject>Spinal cord injury</subject><subject>Therapeutic applications</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0DlLBDEUwPEgiuvVWUsawcJZX-6ZUhaPBQ_wwHLI5lgjc6zJTOG3N-KqrVUC-b1H-CN0SGBKoKzOXsd2SoGQKaFkA-0QIVShOKWb-Q6cFcA4naDdlN4ACBNSbaMJpaSkFMod9PIYGteZ0C1x73EbHihoPE94FkcTdIN9H_HdsiPFrbNBD87iOzfGfhX7wZkh9B0OHZ53b2PMT4-r0OWZWR_tPtryuknuYH3uoefLi6fZdXFzfzWfnd8Uhgk-FJbxCogurRSEL5TllfdS0MqDVRIWutJOeQ5MWvBWKVGWeqE1UCWVMYQB20Mn33vzj95Hl4a6Dcm4ptGd68dUE6BcSlZx9g9KSialJCLT029qYp9SdL5exdDq-JFR_VW9ztXrr-p1rp750XrzuGid_cU_mTM4XgOdjG581Dl5-nOSigoEY5_-h4gL</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Jee, Min Ki</creator><creator>Jung, Jin Sun</creator><creator>Im, Young Bin</creator><creator>Jung, Sung Jun</creator><creator>Kang, Soo Kyung</creator><general>Liebert</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20120501</creationdate><title>Silencing of miR20a Is Crucial for Ngn1-Mediated Neuroprotection in Injured Spinal Cord</title><author>Jee, Min Ki ; Jung, Jin Sun ; Im, Young Bin ; Jung, Sung Jun ; Kang, Soo Kyung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-d34901a8d6514b7d49ff6529f0d760ba9ae7f4036d0fd77588abaa02767cc1303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Basic Helix-Loop-Helix Transcription Factors - administration & dosage</topic><topic>Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cell survival</topic><topic>Cell Survival - genetics</topic><topic>Degeneration</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation - genetics</topic><topic>Gene therapy</topic><topic>Health. Pharmaceutical industry</topic><topic>Hindlimb - pathology</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Inflammation</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>MicroRNAs - antagonists & inhibitors</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Motor neurons</topic><topic>Motor Neurons - metabolism</topic><topic>Motor Neurons - pathology</topic><topic>Myelin</topic><topic>Myelin Sheath - pathology</topic><topic>Nerve Tissue Proteins - administration & dosage</topic><topic>Nerve Tissue Proteins - antagonists & inhibitors</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurogenesis</topic><topic>neurogenin 1</topic><topic>Neuroprotection</topic><topic>Regeneration</topic><topic>RNA Interference</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - pathology</topic><topic>Spinal Cord Injuries - metabolism</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - therapy</topic><topic>Spinal cord injury</topic><topic>Therapeutic applications</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jee, Min Ki</creatorcontrib><creatorcontrib>Jung, Jin Sun</creatorcontrib><creatorcontrib>Im, Young Bin</creatorcontrib><creatorcontrib>Jung, Sung Jun</creatorcontrib><creatorcontrib>Kang, Soo Kyung</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jee, Min Ki</au><au>Jung, Jin Sun</au><au>Im, Young Bin</au><au>Jung, Sung Jun</au><au>Kang, Soo Kyung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing of miR20a Is Crucial for Ngn1-Mediated Neuroprotection in Injured Spinal Cord</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>23</volume><issue>5</issue><spage>508</spage><epage>520</epage><pages>508-520</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><coden>HGTHE3</coden><abstract>MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI). In the current study, we focused on miR20a, which causes continuing motor neuron degeneration when overexpressed in SCI lesions. Blocking miR20a in SCI animals led to neural cell survival and eventual neurogenesis with rescued expression of the key target gene, neurogenin 1 (Ngn1). Infusion of siNgn1 resulted in functional deficit in the hindlimbs caused by aggressive secondary injury and actively enhanced the inflammation involved in secondary injury progression. The events involving miR20a underlie motor neuron and myelin destruction and pathophysiology and ultimately block regeneration in injured spinal cords. Inhibition of miR20a expression effectively induced definitive motor neuron survival and neurogenesis, and SCI animals showed improved functional deficit. In this study, we showed that abnormal expression of miR20a induces secondary injury, which suggests that miR20a could be a potential target for therapeutic intervention following SCI.</abstract><cop>Larchmont, NY</cop><pub>Liebert</pub><pmid>22182208</pmid><doi>10.1089/hum.2011.121</doi><tpages>13</tpages></addata></record> |
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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Basic Helix-Loop-Helix Transcription Factors - administration & dosage Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors Basic Helix-Loop-Helix Transcription Factors - metabolism Biological and medical sciences Biotechnology Cell survival Cell Survival - genetics Degeneration Disease Models, Animal Female Fundamental and applied biological sciences. Psychology Gene Expression Regulation - genetics Gene therapy Health. Pharmaceutical industry Hindlimb - pathology Humans Industrial applications and implications. Economical aspects Inflammation Medical sciences Mice MicroRNAs - antagonists & inhibitors MicroRNAs - genetics miRNA Motor neurons Motor Neurons - metabolism Motor Neurons - pathology Myelin Myelin Sheath - pathology Nerve Tissue Proteins - administration & dosage Nerve Tissue Proteins - antagonists & inhibitors Nerve Tissue Proteins - metabolism Neurogenesis neurogenin 1 Neuroprotection Regeneration RNA Interference Spinal Cord - metabolism Spinal Cord - pathology Spinal Cord Injuries - metabolism Spinal Cord Injuries - pathology Spinal Cord Injuries - therapy Spinal cord injury Therapeutic applications Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | Silencing of miR20a Is Crucial for Ngn1-Mediated Neuroprotection in Injured Spinal Cord |
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