Regulation of zebrafish heart regeneration by miR-133
Zebrafish regenerate cardiac muscle after severe injuries through the activation and proliferation of spared cardiomyocytes. Little is known about factors that control these events. Here we investigated the extent to which miRNAs regulate zebrafish heart regeneration. Microarray analysis identified...
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| Veröffentlicht in: | Developmental biology 2012-05, Vol.365 (2), p.319-327 |
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| creator | Yin, Viravuth P. Lepilina, Alexandra Smith, Ashley Poss, Kenneth D. |
| description | Zebrafish regenerate cardiac muscle after severe injuries through the activation and proliferation of spared cardiomyocytes. Little is known about factors that control these events. Here we investigated the extent to which miRNAs regulate zebrafish heart regeneration. Microarray analysis identified many miRNAs with increased or reduced levels during regeneration. miR-133, a miRNA with known roles in cardiac development and disease, showed diminished expression during regeneration. Induced transgenic elevation of miR-133 levels after injury inhibited myocardial regeneration, while transgenic miR-133 depletion enhanced cardiomyocyte proliferation. Expression analyses indicated that cell cycle factors mps1, cdc37, and PA2G4, and cell junction components cx43 and cldn5, are miR-133 targets during regeneration. Using pharmacological inhibition and EGFP sensor interaction studies, we found that cx43 is a new miR-133 target and regeneration gene. Our results reveal dynamic regulation of miRNAs during heart regeneration, and indicate that miR-133 restricts injury-induced cardiomyocyte proliferation.
► Functionally dissected miRNA contributions during cardiac regeneration. ► Developed inducible transgenic technology to modulate miRNA function. ► Modulation of miR-133 toggles between cardiac regeneration and scar formation. ► Identified cx43 as new cardiac regeneration gene and direct target of miR-133. |
| doi_str_mv | 10.1016/j.ydbio.2012.02.018 |
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► Functionally dissected miRNA contributions during cardiac regeneration. ► Developed inducible transgenic technology to modulate miRNA function. ► Modulation of miR-133 toggles between cardiac regeneration and scar formation. ► Identified cx43 as new cardiac regeneration gene and direct target of miR-133.</description><identifier>ISSN: 0012-1606</identifier><identifier>EISSN: 1095-564X</identifier><identifier>DOI: 10.1016/j.ydbio.2012.02.018</identifier><identifier>PMID: 22374218</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; cardiomyocytes ; cell cycle ; Cell Proliferation ; Danio rerio ; Freshwater ; genes ; genetically modified organisms ; Heart ; Heart - physiology ; Heart Injuries - physiopathology ; intercellular junctions ; microarray technology ; microRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miR-133 ; Myocytes, Cardiac - physiology ; Oligonucleotide Array Sequence Analysis ; Regeneration ; Transgenes ; Zebrafish ; Zebrafish - physiology</subject><ispartof>Developmental biology, 2012-05, Vol.365 (2), p.319-327</ispartof><rights>2012</rights><rights>Copyright © 2012. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c665t-19bdadfd97454469d275bcc228d21bed31cf7b47dfc257cb7e5529c7025102c23</citedby><cites>FETCH-LOGICAL-c665t-19bdadfd97454469d275bcc228d21bed31cf7b47dfc257cb7e5529c7025102c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0012160612000875$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22374218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yin, Viravuth P.</creatorcontrib><creatorcontrib>Lepilina, Alexandra</creatorcontrib><creatorcontrib>Smith, Ashley</creatorcontrib><creatorcontrib>Poss, Kenneth D.</creatorcontrib><title>Regulation of zebrafish heart regeneration by miR-133</title><title>Developmental biology</title><addtitle>Dev Biol</addtitle><description>Zebrafish regenerate cardiac muscle after severe injuries through the activation and proliferation of spared cardiomyocytes. Little is known about factors that control these events. Here we investigated the extent to which miRNAs regulate zebrafish heart regeneration. Microarray analysis identified many miRNAs with increased or reduced levels during regeneration. miR-133, a miRNA with known roles in cardiac development and disease, showed diminished expression during regeneration. Induced transgenic elevation of miR-133 levels after injury inhibited myocardial regeneration, while transgenic miR-133 depletion enhanced cardiomyocyte proliferation. Expression analyses indicated that cell cycle factors mps1, cdc37, and PA2G4, and cell junction components cx43 and cldn5, are miR-133 targets during regeneration. Using pharmacological inhibition and EGFP sensor interaction studies, we found that cx43 is a new miR-133 target and regeneration gene. Our results reveal dynamic regulation of miRNAs during heart regeneration, and indicate that miR-133 restricts injury-induced cardiomyocyte proliferation.
► Functionally dissected miRNA contributions during cardiac regeneration. ► Developed inducible transgenic technology to modulate miRNA function. ► Modulation of miR-133 toggles between cardiac regeneration and scar formation. ► Identified cx43 as new cardiac regeneration gene and direct target of miR-133.</description><subject>Animals</subject><subject>cardiomyocytes</subject><subject>cell cycle</subject><subject>Cell Proliferation</subject><subject>Danio rerio</subject><subject>Freshwater</subject><subject>genes</subject><subject>genetically modified organisms</subject><subject>Heart</subject><subject>Heart - physiology</subject><subject>Heart Injuries - physiopathology</subject><subject>intercellular junctions</subject><subject>microarray technology</subject><subject>microRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miR-133</subject><subject>Myocytes, Cardiac - physiology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Regeneration</subject><subject>Transgenes</subject><subject>Zebrafish</subject><subject>Zebrafish - physiology</subject><issn>0012-1606</issn><issn>1095-564X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkd9rFDEQx4NY7Fn9CwTdR1_2mkk2P_ZBQYpVoSBUC76FbDJ7l2NvU5O9wvnXN-fW0r6oMDAP85kvM3wIeQV0CRTk6Wa5912IS0aBLWkp0E_IAmgraiGbH0_JgpZJDZLKY_I85w2llGvNn5FjxrhqGOgFEZe42g12CnGsYl_9wi7ZPuR1tUabpirhCkdM87zbV9twWQPnL8hRb4eML-_6Cbk6__j97HN98fXTl7MPF7WTUkw1tJ23vvetakTTyNYzJTrnGNOeQYeeg-tV1yjfOyaU6xQKwVqnKBNAmWP8hLyfc6933Ra9w3FKdjDXKWxt2ptog3k8GcParOKN4bxhXDcl4O1dQIo_d5gnsw3Z4TDYEeMuG9CUU922Qv4bVUJzCQ3_j1RKWw2Mgyoon1GXYs4J-_vjgZqDRrMxvzWag0ZDS4EuW68f_n2_88dbAd7MQG-jsasUsrn6VhJkcaw5p4d33s0EFj83AZPJLuDo0IeEbjI-hr-ecAvsHLcp</recordid><startdate>20120515</startdate><enddate>20120515</enddate><creator>Yin, Viravuth P.</creator><creator>Lepilina, Alexandra</creator><creator>Smith, Ashley</creator><creator>Poss, Kenneth D.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>F1W</scope><scope>H95</scope><scope>L.G</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20120515</creationdate><title>Regulation of zebrafish heart regeneration by miR-133</title><author>Yin, Viravuth P. ; Lepilina, Alexandra ; Smith, Ashley ; Poss, Kenneth D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c665t-19bdadfd97454469d275bcc228d21bed31cf7b47dfc257cb7e5529c7025102c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>cardiomyocytes</topic><topic>cell cycle</topic><topic>Cell Proliferation</topic><topic>Danio rerio</topic><topic>Freshwater</topic><topic>genes</topic><topic>genetically modified organisms</topic><topic>Heart</topic><topic>Heart - physiology</topic><topic>Heart Injuries - physiopathology</topic><topic>intercellular junctions</topic><topic>microarray technology</topic><topic>microRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miR-133</topic><topic>Myocytes, Cardiac - physiology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Regeneration</topic><topic>Transgenes</topic><topic>Zebrafish</topic><topic>Zebrafish - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yin, Viravuth P.</creatorcontrib><creatorcontrib>Lepilina, Alexandra</creatorcontrib><creatorcontrib>Smith, Ashley</creatorcontrib><creatorcontrib>Poss, Kenneth D.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</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>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Developmental biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yin, Viravuth P.</au><au>Lepilina, Alexandra</au><au>Smith, Ashley</au><au>Poss, Kenneth D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of zebrafish heart regeneration by miR-133</atitle><jtitle>Developmental biology</jtitle><addtitle>Dev Biol</addtitle><date>2012-05-15</date><risdate>2012</risdate><volume>365</volume><issue>2</issue><spage>319</spage><epage>327</epage><pages>319-327</pages><issn>0012-1606</issn><eissn>1095-564X</eissn><abstract>Zebrafish regenerate cardiac muscle after severe injuries through the activation and proliferation of spared cardiomyocytes. Little is known about factors that control these events. Here we investigated the extent to which miRNAs regulate zebrafish heart regeneration. Microarray analysis identified many miRNAs with increased or reduced levels during regeneration. miR-133, a miRNA with known roles in cardiac development and disease, showed diminished expression during regeneration. Induced transgenic elevation of miR-133 levels after injury inhibited myocardial regeneration, while transgenic miR-133 depletion enhanced cardiomyocyte proliferation. Expression analyses indicated that cell cycle factors mps1, cdc37, and PA2G4, and cell junction components cx43 and cldn5, are miR-133 targets during regeneration. Using pharmacological inhibition and EGFP sensor interaction studies, we found that cx43 is a new miR-133 target and regeneration gene. Our results reveal dynamic regulation of miRNAs during heart regeneration, and indicate that miR-133 restricts injury-induced cardiomyocyte proliferation.
► Functionally dissected miRNA contributions during cardiac regeneration. ► Developed inducible transgenic technology to modulate miRNA function. ► Modulation of miR-133 toggles between cardiac regeneration and scar formation. ► Identified cx43 as new cardiac regeneration gene and direct target of miR-133.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22374218</pmid><doi>10.1016/j.ydbio.2012.02.018</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals; EZB Electronic Journals Library |
| subjects | Animals cardiomyocytes cell cycle Cell Proliferation Danio rerio Freshwater genes genetically modified organisms Heart Heart - physiology Heart Injuries - physiopathology intercellular junctions microarray technology microRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miR-133 Myocytes, Cardiac - physiology Oligonucleotide Array Sequence Analysis Regeneration Transgenes Zebrafish Zebrafish - physiology |
| title | Regulation of zebrafish heart regeneration by miR-133 |
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