LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation
Upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) contributes to aberrant neovascularization in many different diseases. In contrast, LRG1 is not involved in developmental angiogenesis. Here, we investigated the vasculopathic properties of LRG1 by examining its effect on developing retinal...
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MDPI AG
2025-04-01
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| author | Alexandra E. Hoeh Jui-Hsien Chang Ronja S. Mueller Mark Basche Alessandro Fantin Anastasios Sepetis Giulia De Rossi Athina Dritsoula Robin R. Ali Patric Turowski Stephen E. Moss John Greenwood |
| author_facet | Alexandra E. Hoeh Jui-Hsien Chang Ronja S. Mueller Mark Basche Alessandro Fantin Anastasios Sepetis Giulia De Rossi Athina Dritsoula Robin R. Ali Patric Turowski Stephen E. Moss John Greenwood |
| author_sort | Alexandra E. Hoeh |
| collection | DOAJ |
| description | Upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) contributes to aberrant neovascularization in many different diseases. In contrast, LRG1 is not involved in developmental angiogenesis. Here, we investigated the vasculopathic properties of LRG1 by examining its effect on developing retinal blood vessels. By injecting recombinant protein or an expression vector into the mouse retina during vascular development, we showed that exogenous LRG1 reduces pericyte coverage and NG2 expression. It leads to diminished collagen IV sheathing, fewer adhesion and gap junctions, and reduced vessel calibre and vascular density. Moreover, in mouse retinae containing exogenous LRG1, the developing blood–retinal barrier remains more permeable with significantly higher numbers of transcytotic vesicles present in microvascular endothelial cells. These results reveal that exogeneous LRG1 is sufficient to interfere with the maturation of developing retinal vessels and drive vessel development towards a dysfunctional phenotype. These observations deliver further evidence that LRG1 is an angiopathic factor and highlight the therapeutic potential of blocking LRG1 in diseases characterized by pathogenic angiogenesis or vascular remodelling. |
| format | Article |
| id | doaj-art-02eae5e725de4ded879e1bd0237cba78 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-02eae5e725de4ded879e1bd0237cba782025-08-20T02:24:42ZengMDPI AGCells2073-44092025-04-0114859310.3390/cells14080593LRG1 Alters Pericyte Phenotype and Compromises Vascular MaturationAlexandra E. Hoeh0Jui-Hsien Chang1Ronja S. Mueller2Mark Basche3Alessandro Fantin4Anastasios Sepetis5Giulia De Rossi6Athina Dritsoula7Robin R. Ali8Patric Turowski9Stephen E. Moss10John Greenwood11Institute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKDepartment of Biosciences, University of Milan, 20133 Milan, ItalyInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKInstitute of Ophthalmology, University College London, London EC1V 9EL, UKUpregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) contributes to aberrant neovascularization in many different diseases. In contrast, LRG1 is not involved in developmental angiogenesis. Here, we investigated the vasculopathic properties of LRG1 by examining its effect on developing retinal blood vessels. By injecting recombinant protein or an expression vector into the mouse retina during vascular development, we showed that exogenous LRG1 reduces pericyte coverage and NG2 expression. It leads to diminished collagen IV sheathing, fewer adhesion and gap junctions, and reduced vessel calibre and vascular density. Moreover, in mouse retinae containing exogenous LRG1, the developing blood–retinal barrier remains more permeable with significantly higher numbers of transcytotic vesicles present in microvascular endothelial cells. These results reveal that exogeneous LRG1 is sufficient to interfere with the maturation of developing retinal vessels and drive vessel development towards a dysfunctional phenotype. These observations deliver further evidence that LRG1 is an angiopathic factor and highlight the therapeutic potential of blocking LRG1 in diseases characterized by pathogenic angiogenesis or vascular remodelling.https://www.mdpi.com/2073-4409/14/8/593leucine-rich alpha-2-glycoprotein-1 (LRG1)pericyteblood–retinal barrierangiogenesisblood vessel maturation |
| spellingShingle | Alexandra E. Hoeh Jui-Hsien Chang Ronja S. Mueller Mark Basche Alessandro Fantin Anastasios Sepetis Giulia De Rossi Athina Dritsoula Robin R. Ali Patric Turowski Stephen E. Moss John Greenwood LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation Cells leucine-rich alpha-2-glycoprotein-1 (LRG1) pericyte blood–retinal barrier angiogenesis blood vessel maturation |
| title | LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation |
| title_full | LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation |
| title_fullStr | LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation |
| title_full_unstemmed | LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation |
| title_short | LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation |
| title_sort | lrg1 alters pericyte phenotype and compromises vascular maturation |
| topic | leucine-rich alpha-2-glycoprotein-1 (LRG1) pericyte blood–retinal barrier angiogenesis blood vessel maturation |
| url | https://www.mdpi.com/2073-4409/14/8/593 |
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