Feifei Kan, Di Wang, Sijia Li, Yi Gao, Jianwen Wang
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ITGA5 drives angiogenesis in diabetic retinopathy via TAK-1/NF-kB activation.
Diabetic retinopathy is a retinal damage, which causes vision impairment and blindness. Integrin Subunit Alpha 5 (ITGA5) regulates angiogenic response, but its roles in diabetic retinopathy remain unclear. In this work, diabetes mellitus was induced in rats by streptozotocin. ITGA5 interference was achieved by intravitreal delivery of adeno-associated virus. Upregulation of ITGA5 was found in diabetic rat retinal tissues. ITGA5 knockdown decreased the neovascularization, acellular capillary formation, and pericytes. The protein expression of vascular endothelial growth factor (VEGFA), vascular adhesion molecule-1(VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was reduced after ITGA5 interference. Besides, ITGA5 knockdown decreased the phosphorylation level of FAK, TAK-1, and p65. In vitro, rat retinal microvascular endothelial cells (RRMECs) were cultured under high glucose condition to stimulate diabetic environment. ITGA5 knockdown inhibited VEGFA secretion, tube formation, cell invasion, and migration. Upregulation of VCAM-1 and ICAM-1 that induced by high glucose was reversed by ITGA5 silencing. ITGA5 knockdown blocked the activation of TAK-1/NF-kB pathway in RRMECs. Additionally, in oxygen-induced retinopathy model, ITGA5 interference inhibited pathological neovascularization. These results demonstrate that ITGA5 contributes to the angiogenesis in diabetic retinopathy by activating TAK-1/NF-kB pathway.
期刊介绍：
Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well.
Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format.
Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
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