Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway
Complement factor B (CFB), a 95-kDa protein, is a crucial catalytic element of the alternative pathway (AP) of complement. After binding of CFB to C3b, activation of the AP depends on the proteolytic cleavage of CFB by factor D to generate the C3 convertase (C3bBb). The C3 convertase contains the ca...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/154019 |
| _version_ | 1826111222506848256 |
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| author | Murray, Hannah Qiu, Beiying Ho, Sze Yuan Wang, Xiaomeng |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Murray, Hannah Qiu, Beiying Ho, Sze Yuan Wang, Xiaomeng |
| author_sort | Murray, Hannah |
| collection | NTU |
| description | Complement factor B (CFB), a 95-kDa protein, is a crucial catalytic element of the alternative pathway (AP) of complement. After binding of CFB to C3b, activation of the AP depends on the proteolytic cleavage of CFB by factor D to generate the C3 convertase (C3bBb). The C3 convertase contains the catalytic subunit of CFB (Bb), the enzymatic site for the cleavage of a new molecule of C3 into C3b. In addition to its role in activating the AP, CFB has been implicated in pathological ocular neovascularization, a common feature of several blinding eye diseases, however, with somewhat conflicting results. The focus of this study was to investigate the direct impact of CFB on ocular neovascularization in a tightly controlled environment. Using mouse models of laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), our study demonstrated an increase in CFB expression during pathological angiogenesis. Results from several in vitro and ex vivo functionality assays indicated a promoting effect of CFB in angiogenesis. Mechanistically, CFB exerts this pro-angiogenic effect by mediating the vascular endothelial growth factor (VEGF) signaling pathway. In summary, we demonstrate compelling evidence for the role of CFB in driving ocular angiogenesis in a VEGF-dependent manner. This work provides a framework for a more in-depth exploration of CFB-mediated effects in ocular angiogenesis in the future. |
| first_indexed | 2024-10-01T02:47:08Z |
| format | Journal Article |
| id | ntu-10356/154019 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:47:08Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1540192023-03-05T16:51:22Z Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway Murray, Hannah Qiu, Beiying Ho, Sze Yuan Wang, Xiaomeng Lee Kong Chian School of Medicine (LKCMedicine) Singapore Eye Research Institute Duke-NUS Graduate Medical School Science::Medicine Complement Factor B Angiogenesis Complement factor B (CFB), a 95-kDa protein, is a crucial catalytic element of the alternative pathway (AP) of complement. After binding of CFB to C3b, activation of the AP depends on the proteolytic cleavage of CFB by factor D to generate the C3 convertase (C3bBb). The C3 convertase contains the catalytic subunit of CFB (Bb), the enzymatic site for the cleavage of a new molecule of C3 into C3b. In addition to its role in activating the AP, CFB has been implicated in pathological ocular neovascularization, a common feature of several blinding eye diseases, however, with somewhat conflicting results. The focus of this study was to investigate the direct impact of CFB on ocular neovascularization in a tightly controlled environment. Using mouse models of laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), our study demonstrated an increase in CFB expression during pathological angiogenesis. Results from several in vitro and ex vivo functionality assays indicated a promoting effect of CFB in angiogenesis. Mechanistically, CFB exerts this pro-angiogenic effect by mediating the vascular endothelial growth factor (VEGF) signaling pathway. In summary, we demonstrate compelling evidence for the role of CFB in driving ocular angiogenesis in a VEGF-dependent manner. This work provides a framework for a more in-depth exploration of CFB-mediated effects in ocular angiogenesis in the future. Ministry of Education (MOE) National Medical Research Council (NMRC) Published version This research was funded by the Ministry of Education Singapore Tier 1 grant (2017- T1-001-099) to X.W., Singapore Biomedical Research Council SPF grant (SIPRAD) to X.W., Singapore National Medical Research Council DYNAMO NMRC/OFLCG/001/2017 to X.W. and TAAP NMRC/OFLCG/004/2018 to X.W. 2022-06-08T00:32:02Z 2022-06-08T00:32:02Z 2021 Journal Article Murray, H., Qiu, B., Ho, S. Y. & Wang, X. (2021). Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway. International Journal of Molecular Sciences, 22(17), 9580-. https://dx.doi.org/10.3390/ijms22179580 1661-6596 https://hdl.handle.net/10356/154019 10.3390/ijms22179580 34502486 2-s2.0-85114256573 17 22 9580 en 2017T1-001-099 DYNAMO NMRC/OFLCG/001/2017 TAAP NMRC/OFLCG/004/2018 International Journal of Molecular Sciences © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). application/pdf |
| spellingShingle | Science::Medicine Complement Factor B Angiogenesis Murray, Hannah Qiu, Beiying Ho, Sze Yuan Wang, Xiaomeng Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway |
| title | Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway |
| title_full | Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway |
| title_fullStr | Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway |
| title_full_unstemmed | Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway |
| title_short | Complement factor B mediates ocular angiogenesis through regulating the VEGF signaling pathway |
| title_sort | complement factor b mediates ocular angiogenesis through regulating the vegf signaling pathway |
| topic | Science::Medicine Complement Factor B Angiogenesis |
| url | https://hdl.handle.net/10356/154019 |
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