Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering
Background Organs and tissues need to be vascularized during development. Similarly, vascularization is required to engineer thick tissues. How vessels are formed during organogenesis is not fully understood, and vascularization of engineered tissues remains a significant challenge. Methods and Resu...
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Wiley
2025-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.037943 |
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| author | Chinmoy Patra Amey Rayrikar Ganesh Wagh Florian Kleefeldt Kaveh Roshanbinfar Florian Cop Iva Nikolic Mirko H. H. Schmidt Amparo Acker‐Palmer Süleyman Ergün Felix B. Engel |
| author_facet | Chinmoy Patra Amey Rayrikar Ganesh Wagh Florian Kleefeldt Kaveh Roshanbinfar Florian Cop Iva Nikolic Mirko H. H. Schmidt Amparo Acker‐Palmer Süleyman Ergün Felix B. Engel |
| author_sort | Chinmoy Patra |
| collection | DOAJ |
| description | Background Organs and tissues need to be vascularized during development. Similarly, vascularization is required to engineer thick tissues. How vessels are formed during organogenesis is not fully understood, and vascularization of engineered tissues remains a significant challenge. Methods and Results Here, we show that the extracellular matrix protein nephronectin is required for vascularization during zebrafish development as well as adult fin regeneration and is sufficient to promote mammalian vessel formation and maturation. Nephronectin a morphants and mutants exhibit diminished axial vein sprouting and posterior intersegmental vessel growth. Notably, the angiogenesis‐associated integrins itgav and itgb3.1 are coexpressed with nephronectin a in the region of the caudal vein plexus and posterior somites; nephronectin binds to integrin alpha‐V/integrin beta‐3.1 (ITGAV/ITGB3.1), and itgav morphants phenocopy nephronectin a mutants. In addition, nephronectin a mutants showed decreased vessel maturation compared with wild‐type siblings during caudal fin regeneration in adult zebrafish. Moreover, nephronectin promotes mammalian endothelial cell migration and tube formation in 2D and 3‐dimensional in vitro tissue culture. Further, nephronectin enhances vascular endothelial growth factor‐induced periaortic vascular capillary interconnectivity, vessel diameter, and vessel stability. Conclusions Collectively, our results identify nephronectin as a proangiogenic factor during embryonic development, which can be used to improve the vascularization of engineered tissues. |
| format | Article |
| id | doaj-art-a28f96965c9a4e049e1c9f3facfcacd1 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-a28f96965c9a4e049e1c9f3facfcacd12025-02-04T11:00:01ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-02-0114310.1161/JAHA.123.037943Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue EngineeringChinmoy Patra0Amey Rayrikar1Ganesh Wagh2Florian Kleefeldt3Kaveh Roshanbinfar4Florian Cop5Iva Nikolic6Mirko H. H. Schmidt7Amparo Acker‐Palmer8Süleyman Ergün9Felix B. Engel10Department of Developmental Biology Agharkar Research Institute Pune IndiaDepartment of Developmental Biology Agharkar Research Institute Pune IndiaDepartment of Developmental Biology Agharkar Research Institute Pune IndiaInstitute of Anatomy and Cell Biology II Julius‐Maximilians‐University Würzburg GermanyExperimental Renal and Cardiovascular Research, Department of Nephropathology Institute of Pathology and Department of Cardiology Friedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU) Erlangen GermanyInstitute of Cell Biology and Neuroscience Johann Wolfgang Goethe University Frankfurt am Main Frankfurt am Main GermanyDepartment of Biochemistry and Molecular Biology Monash Biomedicine Discovery Institute Monash University Clayton AustraliaInstitute of Anatomy, Medical Faculty Carl Gustav Carus Technische Universität Dresden School of Medicine Dresden GermanyInstitute of Cell Biology and Neuroscience Johann Wolfgang Goethe University Frankfurt am Main Frankfurt am Main GermanyInstitute of Anatomy and Cell Biology II Julius‐Maximilians‐University Würzburg GermanyExperimental Renal and Cardiovascular Research, Department of Nephropathology Institute of Pathology and Department of Cardiology Friedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU) Erlangen GermanyBackground Organs and tissues need to be vascularized during development. Similarly, vascularization is required to engineer thick tissues. How vessels are formed during organogenesis is not fully understood, and vascularization of engineered tissues remains a significant challenge. Methods and Results Here, we show that the extracellular matrix protein nephronectin is required for vascularization during zebrafish development as well as adult fin regeneration and is sufficient to promote mammalian vessel formation and maturation. Nephronectin a morphants and mutants exhibit diminished axial vein sprouting and posterior intersegmental vessel growth. Notably, the angiogenesis‐associated integrins itgav and itgb3.1 are coexpressed with nephronectin a in the region of the caudal vein plexus and posterior somites; nephronectin binds to integrin alpha‐V/integrin beta‐3.1 (ITGAV/ITGB3.1), and itgav morphants phenocopy nephronectin a mutants. In addition, nephronectin a mutants showed decreased vessel maturation compared with wild‐type siblings during caudal fin regeneration in adult zebrafish. Moreover, nephronectin promotes mammalian endothelial cell migration and tube formation in 2D and 3‐dimensional in vitro tissue culture. Further, nephronectin enhances vascular endothelial growth factor‐induced periaortic vascular capillary interconnectivity, vessel diameter, and vessel stability. Conclusions Collectively, our results identify nephronectin as a proangiogenic factor during embryonic development, which can be used to improve the vascularization of engineered tissues.https://www.ahajournals.org/doi/10.1161/JAHA.123.037943extracellular matrixnephronectintissue engineeringvascularizationzebrafish |
| spellingShingle | Chinmoy Patra Amey Rayrikar Ganesh Wagh Florian Kleefeldt Kaveh Roshanbinfar Florian Cop Iva Nikolic Mirko H. H. Schmidt Amparo Acker‐Palmer Süleyman Ergün Felix B. Engel Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease extracellular matrix nephronectin tissue engineering vascularization zebrafish |
| title | Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering |
| title_full | Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering |
| title_fullStr | Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering |
| title_full_unstemmed | Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering |
| title_short | Nephronectin Is Required for Vascularization in Zebrafish and Sufficient to Promote Mammalian Vessel‐Like Structures in Hydrogels for Tissue Engineering |
| title_sort | nephronectin is required for vascularization in zebrafish and sufficient to promote mammalian vessel like structures in hydrogels for tissue engineering |
| topic | extracellular matrix nephronectin tissue engineering vascularization zebrafish |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.037943 |
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