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HAX1-Overexpression Augments Cardioprotective Efficacy of Stem Cell-Based Therapy Through Mediating Hippo-Yap Signaling
Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective si...
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| Published in: | Stem cell reviews and reports 2024-08, Vol.20 (6), p.1569-1586 |
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| creator | Cai, Wen-Feng Jiang, Lin Liang, Jialiang Dutta, Suchandrima Huang, Wei He, Xingyu Wu, Zhichao Paul, Christian Gao, Xiang Xu, Meifeng Kanisicak, Onur Zheng, Junmeng Wang, Yigang |
| description | Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective signaling, while its role in regulating stem cell survival and functionality remains unknown. In this study, we investigated whether HAX1 can augment the protective potential of Sca1
+
cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.
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| doi_str_mv | 10.1007/s12015-024-10729-z |
| format | article |
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+
cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.
Graphical Abstract</description><identifier>ISSN: 2629-3269</identifier><identifier>ISSN: 2629-3277</identifier><identifier>EISSN: 2629-3277</identifier><identifier>DOI: 10.1007/s12015-024-10729-z</identifier><identifier>PMID: 38713406</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Angiogenesis ; Ataxin ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Cell Biology ; Cell death ; Cell proliferation ; Cell survival ; Cell therapy ; Fibrosis ; Growth factors ; Heart ; Hypoxia ; Ischemia ; Kinases ; Life Sciences ; Myocardial infarction ; Nuclear transport ; Phosphorylation ; Progenitor cells ; Protein transport ; Protein X ; Proteins ; Regenerative Medicine/Tissue Engineering ; Signal transduction ; Stem Cells ; Stromal cells ; Transcription activation ; Vascularization ; Yes-associated protein</subject><ispartof>Stem cell reviews and reports, 2024-08, Vol.20 (6), p.1569-1586</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-1480fbb04047ad05da718f5f1673bad2d78ce87192cf6bfa181c28606b7a85253</cites><orcidid>0000-0002-0872-1860</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38713406$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Wen-Feng</creatorcontrib><creatorcontrib>Jiang, Lin</creatorcontrib><creatorcontrib>Liang, Jialiang</creatorcontrib><creatorcontrib>Dutta, Suchandrima</creatorcontrib><creatorcontrib>Huang, Wei</creatorcontrib><creatorcontrib>He, Xingyu</creatorcontrib><creatorcontrib>Wu, Zhichao</creatorcontrib><creatorcontrib>Paul, Christian</creatorcontrib><creatorcontrib>Gao, Xiang</creatorcontrib><creatorcontrib>Xu, Meifeng</creatorcontrib><creatorcontrib>Kanisicak, Onur</creatorcontrib><creatorcontrib>Zheng, Junmeng</creatorcontrib><creatorcontrib>Wang, Yigang</creatorcontrib><title>HAX1-Overexpression Augments Cardioprotective Efficacy of Stem Cell-Based Therapy Through Mediating Hippo-Yap Signaling</title><title>Stem cell reviews and reports</title><addtitle>Stem Cell Rev and Rep</addtitle><addtitle>Stem Cell Rev Rep</addtitle><description>Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective signaling, while its role in regulating stem cell survival and functionality remains unknown. In this study, we investigated whether HAX1 can augment the protective potential of Sca1
+
cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.
Graphical Abstract</description><subject>Angiogenesis</subject><subject>Ataxin</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Cell Biology</subject><subject>Cell death</subject><subject>Cell proliferation</subject><subject>Cell survival</subject><subject>Cell therapy</subject><subject>Fibrosis</subject><subject>Growth factors</subject><subject>Heart</subject><subject>Hypoxia</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Myocardial infarction</subject><subject>Nuclear transport</subject><subject>Phosphorylation</subject><subject>Progenitor cells</subject><subject>Protein transport</subject><subject>Protein X</subject><subject>Proteins</subject><subject>Regenerative Medicine/Tissue Engineering</subject><subject>Signal transduction</subject><subject>Stem Cells</subject><subject>Stromal cells</subject><subject>Transcription activation</subject><subject>Vascularization</subject><subject>Yes-associated protein</subject><issn>2629-3269</issn><issn>2629-3277</issn><issn>2629-3277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kUFv1DAQhS0EolXpH-gBWeLCxeCxkzg5oWVVWKSiHlokerIcx866SuJgJ1u2vx4vW5aWA6cZeb55nqeH0BnQd0CpeB-BUcgJZRkBKlhF7p-hY1akhjMhnh_6ojpCpzHeUkoZp1naeYmOeCmAZ7Q4RnerxXcglxsTzM8xmBidH_BibnszTBEvVWicH4OfjJ7cxuBza51Weou9xVeT6fHSdB35qKJp8PXaBDVuUw1-btf4q2mcmtzQ4pUbR09u1IivXDuoLr29Qi-s6qI5fagn6Nun8-vlilxcfv6yXFwQnbFiIpCV1NZ1ujsTqqF5owSUNrdQCF6rhjWi1CaZqZi2RW0VlKBZWdCiFqrMWc5P0Ie97jjXvWl0shVUJ8fgehW20isnn04Gt5at30gADhWvWFJ4-6AQ_I_ZxEn2LupkWw3Gz1Fymu9AyCChb_5Bb_0ckuEdVTHgZcVFotie0sHHGIw9XANU7rKV-2xlylb-zlbep6XXj30cVv4kmQC-B2IaDa0Jf__-j-wvjfiwrw</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Cai, Wen-Feng</creator><creator>Jiang, Lin</creator><creator>Liang, Jialiang</creator><creator>Dutta, Suchandrima</creator><creator>Huang, Wei</creator><creator>He, Xingyu</creator><creator>Wu, Zhichao</creator><creator>Paul, Christian</creator><creator>Gao, Xiang</creator><creator>Xu, Meifeng</creator><creator>Kanisicak, Onur</creator><creator>Zheng, Junmeng</creator><creator>Wang, Yigang</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0872-1860</orcidid></search><sort><creationdate>20240801</creationdate><title>HAX1-Overexpression Augments Cardioprotective Efficacy of Stem Cell-Based Therapy Through Mediating Hippo-Yap Signaling</title><author>Cai, Wen-Feng ; Jiang, Lin ; Liang, Jialiang ; Dutta, Suchandrima ; Huang, Wei ; He, Xingyu ; Wu, Zhichao ; Paul, Christian ; Gao, Xiang ; Xu, Meifeng ; Kanisicak, Onur ; Zheng, Junmeng ; Wang, Yigang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-1480fbb04047ad05da718f5f1673bad2d78ce87192cf6bfa181c28606b7a85253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis</topic><topic>Ataxin</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Cell Biology</topic><topic>Cell death</topic><topic>Cell proliferation</topic><topic>Cell survival</topic><topic>Cell therapy</topic><topic>Fibrosis</topic><topic>Growth factors</topic><topic>Heart</topic><topic>Hypoxia</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Myocardial infarction</topic><topic>Nuclear transport</topic><topic>Phosphorylation</topic><topic>Progenitor cells</topic><topic>Protein transport</topic><topic>Protein X</topic><topic>Proteins</topic><topic>Regenerative Medicine/Tissue Engineering</topic><topic>Signal transduction</topic><topic>Stem Cells</topic><topic>Stromal cells</topic><topic>Transcription activation</topic><topic>Vascularization</topic><topic>Yes-associated protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Wen-Feng</creatorcontrib><creatorcontrib>Jiang, Lin</creatorcontrib><creatorcontrib>Liang, Jialiang</creatorcontrib><creatorcontrib>Dutta, Suchandrima</creatorcontrib><creatorcontrib>Huang, Wei</creatorcontrib><creatorcontrib>He, Xingyu</creatorcontrib><creatorcontrib>Wu, Zhichao</creatorcontrib><creatorcontrib>Paul, Christian</creatorcontrib><creatorcontrib>Gao, Xiang</creatorcontrib><creatorcontrib>Xu, Meifeng</creatorcontrib><creatorcontrib>Kanisicak, Onur</creatorcontrib><creatorcontrib>Zheng, Junmeng</creatorcontrib><creatorcontrib>Wang, Yigang</creatorcontrib><collection>SpringerOpen (Open Access)</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cell reviews and reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Wen-Feng</au><au>Jiang, Lin</au><au>Liang, Jialiang</au><au>Dutta, Suchandrima</au><au>Huang, Wei</au><au>He, Xingyu</au><au>Wu, Zhichao</au><au>Paul, Christian</au><au>Gao, Xiang</au><au>Xu, Meifeng</au><au>Kanisicak, Onur</au><au>Zheng, Junmeng</au><au>Wang, Yigang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HAX1-Overexpression Augments Cardioprotective Efficacy of Stem Cell-Based Therapy Through Mediating Hippo-Yap Signaling</atitle><jtitle>Stem cell reviews and reports</jtitle><stitle>Stem Cell Rev and Rep</stitle><addtitle>Stem Cell Rev Rep</addtitle><date>2024-08-01</date><risdate>2024</risdate><volume>20</volume><issue>6</issue><spage>1569</spage><epage>1586</epage><pages>1569-1586</pages><issn>2629-3269</issn><issn>2629-3277</issn><eissn>2629-3277</eissn><abstract>Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective signaling, while its role in regulating stem cell survival and functionality remains unknown. In this study, we investigated whether HAX1 can augment the protective potential of Sca1
+
cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.
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| subjects | Angiogenesis Ataxin Biomedical and Life Sciences Biomedical Engineering and Bioengineering Cell Biology Cell death Cell proliferation Cell survival Cell therapy Fibrosis Growth factors Heart Hypoxia Ischemia Kinases Life Sciences Myocardial infarction Nuclear transport Phosphorylation Progenitor cells Protein transport Protein X Proteins Regenerative Medicine/Tissue Engineering Signal transduction Stem Cells Stromal cells Transcription activation Vascularization Yes-associated protein |
| title | HAX1-Overexpression Augments Cardioprotective Efficacy of Stem Cell-Based Therapy Through Mediating Hippo-Yap Signaling |
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