Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea
Recent studies have reported the role of Wnt/ β -catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/ β -catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifical...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2016-03, Vol.7 (3), p.e2136-e2136 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e2136 |
|---|---|
| container_issue | 3 |
| container_start_page | e2136 |
| container_title | Cell death & disease |
| container_volume | 7 |
| creator | Liu, L Chen, Y Qi, J Zhang, Y He, Y Ni, W Li, W Zhang, S Sun, S Taketo, M M Wang, L Chai, R Li, H |
| description | Recent studies have reported the role of Wnt/
β
-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/
β
-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator
β
-catenin in HCs, which allowed us to investigate the role of Wnt/
β
-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of
β
-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of
β
-catenin in HCs reduced HC loss both
in vivo
and
in vitro
. We then showed that loss of
β
-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while
β
-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of
β
-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast,
β
-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that
β
-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/
β
-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death. |
| doi_str_mv | 10.1038/cddis.2016.35 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4823936</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1772832944</sourcerecordid><originalsourceid>FETCH-LOGICAL-c564t-93000a6d9599c5767e624fdb8ad54827ae77a4a1d9427b1a6b6ab7c87fe20d553</originalsourceid><addsrcrecordid>eNptkc1rFDEYh4MottQevUrAi5dZJx-Tj4sgpdpCwYutx_BOkt1NmUnWJFPof2_WrWUVc0ngffjlffgh9Jb0K9Iz9dE6F8qK9kSs2PACndKek44rpV8evU_QeSn3fTuM9XQQr9EJFVpQocQpuvsRKwZbwwPUkCLe5VS9rQXDBkIsFUef5kcbYheiW6x3eAshY-unCTuYYeNxiLhuPZ7TUjy2yW4nD2_QqzVMxZ8_3Wfo9svl94ur7ubb1-uLzzedHQSvnWZtKxBOD1rbQQrpBeVrNypwA1dUgpcSOBCnOZUjATEKGKVVcu1p74aBnaFPh9zdMs7eWR9rhsnscpghP5oEwfw9iWFrNunBtHSmmWgBH54Ccvq5-FLNHMreDpr4UgyRkipGNecNff8Pep-WHJteo9SgOVFCNao7UDanUrJfPy9DerMvzfwuzexLM2xv8O7Y4Jn-U1EDVgegtFHc-Hz07X8TfwHKo6Ny</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1785941868</pqid></control><display><type>article</type><title>Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea</title><source>Open Access: Nature Open Access</source><source>SpringerOpen</source><source>MEDLINE</source><source>PubMed Central</source><source>Directory of Open Access Journals</source><source>EZB Electronic Journals Library</source><creator>Liu, L ; Chen, Y ; Qi, J ; Zhang, Y ; He, Y ; Ni, W ; Li, W ; Zhang, S ; Sun, S ; Taketo, M M ; Wang, L ; Chai, R ; Li, H</creator><creatorcontrib>Liu, L ; Chen, Y ; Qi, J ; Zhang, Y ; He, Y ; Ni, W ; Li, W ; Zhang, S ; Sun, S ; Taketo, M M ; Wang, L ; Chai, R ; Li, H</creatorcontrib><description>Recent studies have reported the role of Wnt/
β
-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/
β
-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator
β
-catenin in HCs, which allowed us to investigate the role of Wnt/
β
-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of
β
-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of
β
-catenin in HCs reduced HC loss both
in vivo
and
in vitro
. We then showed that loss of
β
-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while
β
-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of
β
-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast,
β
-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that
β
-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/
β
-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/cddis.2016.35</identifier><identifier>PMID: 26962686</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/31 ; 13/51 ; 14/19 ; 38/77 ; 631/378/2619/1533 ; 631/80/82/23 ; 631/80/86 ; 692/700/565/2194 ; 82/51 ; 82/80 ; Animals ; Antibodies ; Apoptosis ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Bcl-2-Like Protein 11 ; beta Catenin - genetics ; beta Catenin - metabolism ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell Death ; Ears & hearing ; Forkhead Box Protein O3 ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Hair Cells, Auditory - metabolism ; Hair Cells, Auditory - pathology ; Hearing Loss - chemically induced ; Hearing Loss - genetics ; Hearing Loss - metabolism ; Hearing Loss - prevention & control ; Immunology ; Life Sciences ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Transgenic ; Neomycin - adverse effects ; Neomycin - pharmacology ; Original ; original-article ; Protein expression ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Reactive Oxygen Species - metabolism ; Rodents ; Signal transduction ; Wnt Signaling Pathway - drug effects ; Wnt Signaling Pathway - genetics</subject><ispartof>Cell death & disease, 2016-03, Vol.7 (3), p.e2136-e2136</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Mar 2016</rights><rights>Copyright © 2016 Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-93000a6d9599c5767e624fdb8ad54827ae77a4a1d9427b1a6b6ab7c87fe20d553</citedby><cites>FETCH-LOGICAL-c564t-93000a6d9599c5767e624fdb8ad54827ae77a4a1d9427b1a6b6ab7c87fe20d553</cites><orcidid>0000-0002-3394-2278</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823936/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823936/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26962686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, L</creatorcontrib><creatorcontrib>Chen, Y</creatorcontrib><creatorcontrib>Qi, J</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>He, Y</creatorcontrib><creatorcontrib>Ni, W</creatorcontrib><creatorcontrib>Li, W</creatorcontrib><creatorcontrib>Zhang, S</creatorcontrib><creatorcontrib>Sun, S</creatorcontrib><creatorcontrib>Taketo, M M</creatorcontrib><creatorcontrib>Wang, L</creatorcontrib><creatorcontrib>Chai, R</creatorcontrib><creatorcontrib>Li, H</creatorcontrib><title>Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Recent studies have reported the role of Wnt/
β
-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/
β
-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator
β
-catenin in HCs, which allowed us to investigate the role of Wnt/
β
-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of
β
-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of
β
-catenin in HCs reduced HC loss both
in vivo
and
in vitro
. We then showed that loss of
β
-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while
β
-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of
β
-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast,
β
-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that
β
-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/
β
-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.</description><subject>13/1</subject><subject>13/31</subject><subject>13/51</subject><subject>14/19</subject><subject>38/77</subject><subject>631/378/2619/1533</subject><subject>631/80/82/23</subject><subject>631/80/86</subject><subject>692/700/565/2194</subject><subject>82/51</subject><subject>82/80</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Bcl-2-Like Protein 11</subject><subject>beta Catenin - genetics</subject><subject>beta Catenin - metabolism</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Death</subject><subject>Ears & hearing</subject><subject>Forkhead Box Protein O3</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Hair Cells, Auditory - metabolism</subject><subject>Hair Cells, Auditory - pathology</subject><subject>Hearing Loss - chemically induced</subject><subject>Hearing Loss - genetics</subject><subject>Hearing Loss - metabolism</subject><subject>Hearing Loss - prevention & control</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neomycin - adverse effects</subject><subject>Neomycin - pharmacology</subject><subject>Original</subject><subject>original-article</subject><subject>Protein expression</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Wnt Signaling Pathway - genetics</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkc1rFDEYh4MottQevUrAi5dZJx-Tj4sgpdpCwYutx_BOkt1NmUnWJFPof2_WrWUVc0ngffjlffgh9Jb0K9Iz9dE6F8qK9kSs2PACndKek44rpV8evU_QeSn3fTuM9XQQr9EJFVpQocQpuvsRKwZbwwPUkCLe5VS9rQXDBkIsFUef5kcbYheiW6x3eAshY-unCTuYYeNxiLhuPZ7TUjy2yW4nD2_QqzVMxZ8_3Wfo9svl94ur7ubb1-uLzzedHQSvnWZtKxBOD1rbQQrpBeVrNypwA1dUgpcSOBCnOZUjATEKGKVVcu1p74aBnaFPh9zdMs7eWR9rhsnscpghP5oEwfw9iWFrNunBtHSmmWgBH54Ccvq5-FLNHMreDpr4UgyRkipGNecNff8Pep-WHJteo9SgOVFCNao7UDanUrJfPy9DerMvzfwuzexLM2xv8O7Y4Jn-U1EDVgegtFHc-Hz07X8TfwHKo6Ny</recordid><startdate>20160310</startdate><enddate>20160310</enddate><creator>Liu, L</creator><creator>Chen, Y</creator><creator>Qi, J</creator><creator>Zhang, Y</creator><creator>He, Y</creator><creator>Ni, W</creator><creator>Li, W</creator><creator>Zhang, S</creator><creator>Sun, S</creator><creator>Taketo, M M</creator><creator>Wang, L</creator><creator>Chai, R</creator><creator>Li, H</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3394-2278</orcidid></search><sort><creationdate>20160310</creationdate><title>Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea</title><author>Liu, L ; Chen, Y ; Qi, J ; Zhang, Y ; He, Y ; Ni, W ; Li, W ; Zhang, S ; Sun, S ; Taketo, M M ; Wang, L ; Chai, R ; Li, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c564t-93000a6d9599c5767e624fdb8ad54827ae77a4a1d9427b1a6b6ab7c87fe20d553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/1</topic><topic>13/31</topic><topic>13/51</topic><topic>14/19</topic><topic>38/77</topic><topic>631/378/2619/1533</topic><topic>631/80/82/23</topic><topic>631/80/86</topic><topic>692/700/565/2194</topic><topic>82/51</topic><topic>82/80</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Bcl-2-Like Protein 11</topic><topic>beta Catenin - genetics</topic><topic>beta Catenin - metabolism</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Death</topic><topic>Ears & hearing</topic><topic>Forkhead Box Protein O3</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Hair Cells, Auditory - metabolism</topic><topic>Hair Cells, Auditory - pathology</topic><topic>Hearing Loss - chemically induced</topic><topic>Hearing Loss - genetics</topic><topic>Hearing Loss - metabolism</topic><topic>Hearing Loss - prevention & control</topic><topic>Immunology</topic><topic>Life Sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neomycin - adverse effects</topic><topic>Neomycin - pharmacology</topic><topic>Original</topic><topic>original-article</topic><topic>Protein expression</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Wnt Signaling Pathway - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, L</creatorcontrib><creatorcontrib>Chen, Y</creatorcontrib><creatorcontrib>Qi, J</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>He, Y</creatorcontrib><creatorcontrib>Ni, W</creatorcontrib><creatorcontrib>Li, W</creatorcontrib><creatorcontrib>Zhang, S</creatorcontrib><creatorcontrib>Sun, S</creatorcontrib><creatorcontrib>Taketo, M M</creatorcontrib><creatorcontrib>Wang, L</creatorcontrib><creatorcontrib>Chai, R</creatorcontrib><creatorcontrib>Li, H</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, L</au><au>Chen, Y</au><au>Qi, J</au><au>Zhang, Y</au><au>He, Y</au><au>Ni, W</au><au>Li, W</au><au>Zhang, S</au><au>Sun, S</au><au>Taketo, M M</au><au>Wang, L</au><au>Chai, R</au><au>Li, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2016-03-10</date><risdate>2016</risdate><volume>7</volume><issue>3</issue><spage>e2136</spage><epage>e2136</epage><pages>e2136-e2136</pages><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Recent studies have reported the role of Wnt/
β
-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/
β
-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator
β
-catenin in HCs, which allowed us to investigate the role of Wnt/
β
-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of
β
-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of
β
-catenin in HCs reduced HC loss both
in vivo
and
in vitro
. We then showed that loss of
β
-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while
β
-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of
β
-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast,
β
-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that
β
-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/
β
-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26962686</pmid><doi>10.1038/cddis.2016.35</doi><orcidid>https://orcid.org/0000-0002-3394-2278</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2016-03, Vol.7 (3), p.e2136-e2136 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4823936 |
| source | Open Access: Nature Open Access; SpringerOpen; MEDLINE; PubMed Central; Directory of Open Access Journals; EZB Electronic Journals Library |
| subjects | 13/1 13/31 13/51 14/19 38/77 631/378/2619/1533 631/80/82/23 631/80/86 692/700/565/2194 82/51 82/80 Animals Antibodies Apoptosis Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Bcl-2-Like Protein 11 beta Catenin - genetics beta Catenin - metabolism Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell Death Ears & hearing Forkhead Box Protein O3 Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Hair Cells, Auditory - metabolism Hair Cells, Auditory - pathology Hearing Loss - chemically induced Hearing Loss - genetics Hearing Loss - metabolism Hearing Loss - prevention & control Immunology Life Sciences Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Transgenic Neomycin - adverse effects Neomycin - pharmacology Original original-article Protein expression Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Reactive Oxygen Species - metabolism Rodents Signal transduction Wnt Signaling Pathway - drug effects Wnt Signaling Pathway - genetics |
| title | Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T08%3A51%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Wnt%20activation%20protects%20against%20neomycin-induced%20hair%20cell%20damage%20in%20the%20mouse%20cochlea&rft.jtitle=Cell%20death%20&%20disease&rft.au=Liu,%20L&rft.date=2016-03-10&rft.volume=7&rft.issue=3&rft.spage=e2136&rft.epage=e2136&rft.pages=e2136-e2136&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/cddis.2016.35&rft_dat=%3Cproquest_pubme%3E1772832944%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1785941868&rft_id=info:pmid/26962686&rfr_iscdi=true |