Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling
Abstract Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy, for which the underlying pathological mechanisms are still poorly understood. Here, we confirm that angiogenic factor 1 with a G patch and FHA domain (AGGF1) is elevated in the diabe...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55970-3 |
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| author | Ying Cheng Man Zhang Chenguang Li Long Su Lingli Fu Shi Wu Chaofei Xu Bei Sun Liming Chen |
| author_facet | Ying Cheng Man Zhang Chenguang Li Long Su Lingli Fu Shi Wu Chaofei Xu Bei Sun Liming Chen |
| author_sort | Ying Cheng |
| collection | DOAJ |
| description | Abstract Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy, for which the underlying pathological mechanisms are still poorly understood. Here, we confirm that angiogenic factor 1 with a G patch and FHA domain (AGGF1) is elevated in the diabetics and induces retinal angiogenesis. Mechanistic investigations demonstrate that HIF-1α directly regulates AGGF1 expression. AGGF1 upregulates the expression of cell cycle proteins by increasing the binding of tumour necrosis factor ligand superfamily member 12 (TNFSF12) to fibroblast -growth -factor-inducible 14 (FN14, TNFRSF12A). Furthermore, targeting AGGF1 attenuates pathological neovascularisation in ischaemic retinopathy. Additionally, we discover that sodium-glucose cotransporter 2 inhibitors (SGLT2i) could inhibit the AGGF1 signalling pathway early to achieve therapeutic effects. Overall, we elucidate the mechanism underlying pathological retinal angiogenesis involved in endothelial AGGF1-dependent events and highlight a therapy for the effective treatment of ischaemic retinopathy. |
| format | Article |
| id | doaj-art-ce1dc822660a4c16a0e69975bad703ff |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ce1dc822660a4c16a0e69975bad703ff2025-02-09T12:44:44ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-55970-3Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signallingYing Cheng0Man Zhang1Chenguang Li2Long Su3Lingli Fu4Shi Wu5Chaofei Xu6Bei Sun7Liming Chen8NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyNHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of EndocrinologyAbstract Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy, for which the underlying pathological mechanisms are still poorly understood. Here, we confirm that angiogenic factor 1 with a G patch and FHA domain (AGGF1) is elevated in the diabetics and induces retinal angiogenesis. Mechanistic investigations demonstrate that HIF-1α directly regulates AGGF1 expression. AGGF1 upregulates the expression of cell cycle proteins by increasing the binding of tumour necrosis factor ligand superfamily member 12 (TNFSF12) to fibroblast -growth -factor-inducible 14 (FN14, TNFRSF12A). Furthermore, targeting AGGF1 attenuates pathological neovascularisation in ischaemic retinopathy. Additionally, we discover that sodium-glucose cotransporter 2 inhibitors (SGLT2i) could inhibit the AGGF1 signalling pathway early to achieve therapeutic effects. Overall, we elucidate the mechanism underlying pathological retinal angiogenesis involved in endothelial AGGF1-dependent events and highlight a therapy for the effective treatment of ischaemic retinopathy.https://doi.org/10.1038/s41467-025-55970-3 |
| spellingShingle | Ying Cheng Man Zhang Chenguang Li Long Su Lingli Fu Shi Wu Chaofei Xu Bei Sun Liming Chen Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling Nature Communications |
| title | Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling |
| title_full | Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling |
| title_fullStr | Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling |
| title_full_unstemmed | Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling |
| title_short | Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling |
| title_sort | endothelial aggf1 promotes retinal angiogenesis by coordinating tnfsf12 fn14 signalling |
| url | https://doi.org/10.1038/s41467-025-55970-3 |
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