Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis
Alzheimer's disease (AD) is often accompanied by retinal lesions, in which Amyloid β (Aβ) is a key mediator. Vascular dysfunction is always associated with the malignant progression of AD, but the precise mechanisms remain poorly understood. The aim of this study is to investigate how Aβ regula...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Immunobiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171298525002311 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839623788650561536 |
|---|---|
| author | Bin Wang Wenwei Li Chaoyang Hong Fangfang Jin Baisheng Xu Zhongwei Guo Shuyang Chen Qi Zhang |
| author_facet | Bin Wang Wenwei Li Chaoyang Hong Fangfang Jin Baisheng Xu Zhongwei Guo Shuyang Chen Qi Zhang |
| author_sort | Bin Wang |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is often accompanied by retinal lesions, in which Amyloid β (Aβ) is a key mediator. Vascular dysfunction is always associated with the malignant progression of AD, but the precise mechanisms remain poorly understood. The aim of this study is to investigate how Aβ regulates retinal angiogenesis in AD models through the LncRNA-XIST/miR-126-5p/VEGF axis. The research results showed that in the retina of AD model mice, the expression of Aβ and miR-126-5p increased, while the expression of LncRNA-XIST and VEGF decreased. In vitro experiments demonstrated that Aβ treatment downregulated LncRNA-XIST and VEGF expression in RF/6 A cells, while upregulating miR-126-5p and significantly suppressing angiogenesis. Overexpression of LncRNA-XIST can reverse the inhibitory effect of Aβ on angiogenesis, while further overexpression of miR-126-5p can counteract the pro-angiogenic effect of LncRNA-XIST. The dual-luciferase reporter assay results showed that Aβ repressed the transcriptional activity of the LncRNA-XIST promoter by targeting the −800 to −600 fragment. Mechanism studies have revealed that LncRNA-XIST competitively binds to miR-126-5p, preventing its binding to VEGF mRNA and upregulating VEGF expression. In vivo experiments demonstrated that miR-126-5p inhibitor resulted in elevated expression of LncRNA-XIST and VEGF in the mouse retina. This study reveals the molecular mechanism by which Aβ regulates retinal angiogenesis in AD models through the LncRNA-XIST/miR-126-5p/VEGF axis, providing a potential new strategy for targeted therapy of AD-related retinal lesions. |
| format | Article |
| id | doaj-art-9c78f00e7a3843d5b6d1a75d00b4753a |
| institution | Matheson Library |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Immunobiology |
| spelling | doaj-art-9c78f00e7a3843d5b6d1a75d00b4753a2025-07-19T04:37:48ZengElsevierImmunobiology0171-29852025-07-012304153097Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axisBin Wang0Wenwei Li1Chaoyang Hong2Fangfang Jin3Baisheng Xu4Zhongwei Guo5Shuyang Chen6Qi Zhang7The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China; Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, ChinaZhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China; Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China; Corresponding author at: Zhejiang Academy of Traditional Chinese Medicine, No. 234, Gucui Road, Xihu district, Hangzhou, Zhejiang Province, China.Eye Center of Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, ChinaThe Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaZhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China; Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, ChinaZhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China; Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, ChinaZhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China; Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, ChinaEye Center of the Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, ChinaAlzheimer's disease (AD) is often accompanied by retinal lesions, in which Amyloid β (Aβ) is a key mediator. Vascular dysfunction is always associated with the malignant progression of AD, but the precise mechanisms remain poorly understood. The aim of this study is to investigate how Aβ regulates retinal angiogenesis in AD models through the LncRNA-XIST/miR-126-5p/VEGF axis. The research results showed that in the retina of AD model mice, the expression of Aβ and miR-126-5p increased, while the expression of LncRNA-XIST and VEGF decreased. In vitro experiments demonstrated that Aβ treatment downregulated LncRNA-XIST and VEGF expression in RF/6 A cells, while upregulating miR-126-5p and significantly suppressing angiogenesis. Overexpression of LncRNA-XIST can reverse the inhibitory effect of Aβ on angiogenesis, while further overexpression of miR-126-5p can counteract the pro-angiogenic effect of LncRNA-XIST. The dual-luciferase reporter assay results showed that Aβ repressed the transcriptional activity of the LncRNA-XIST promoter by targeting the −800 to −600 fragment. Mechanism studies have revealed that LncRNA-XIST competitively binds to miR-126-5p, preventing its binding to VEGF mRNA and upregulating VEGF expression. In vivo experiments demonstrated that miR-126-5p inhibitor resulted in elevated expression of LncRNA-XIST and VEGF in the mouse retina. This study reveals the molecular mechanism by which Aβ regulates retinal angiogenesis in AD models through the LncRNA-XIST/miR-126-5p/VEGF axis, providing a potential new strategy for targeted therapy of AD-related retinal lesions.http://www.sciencedirect.com/science/article/pii/S0171298525002311Alzheimer's diseaseRetinopathyAmyloid βLncRNA-XISTmiR-126-5pVEGF |
| spellingShingle | Bin Wang Wenwei Li Chaoyang Hong Fangfang Jin Baisheng Xu Zhongwei Guo Shuyang Chen Qi Zhang Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis Immunobiology Alzheimer's disease Retinopathy Amyloid β LncRNA-XIST miR-126-5p VEGF |
| title | Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis |
| title_full | Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis |
| title_fullStr | Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis |
| title_full_unstemmed | Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis |
| title_short | Amyloid β (Aβ) inhibits retinal angiogenesis in Alzheimer's disease via LncRNA-XIST/miRNA-126-5p/VEGF axis |
| title_sort | amyloid β aβ inhibits retinal angiogenesis in alzheimer s disease via lncrna xist mirna 126 5p vegf axis |
| topic | Alzheimer's disease Retinopathy Amyloid β LncRNA-XIST miR-126-5p VEGF |
| url | http://www.sciencedirect.com/science/article/pii/S0171298525002311 |
| work_keys_str_mv | AT binwang amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT wenweili amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT chaoyanghong amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT fangfangjin amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT baishengxu amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT zhongweiguo amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT shuyangchen amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis AT qizhang amyloidbabinhibitsretinalangiogenesisinalzheimersdiseasevialncrnaxistmirna1265pvegfaxis |