Targeting TRAF7 to Enhance Angiogenesis and Mitigate Ischemia-Induced Brain Damage: Insights from in Vivo and in Vitro Models

Nianping Feng, Yun Wu, Haihong Zheng, Jingjing Ji, Genjie Li, Yushan Li, Yuexin Guan, Xingjun Xiao, Zhuo Zhang

Article ID: 7863
Vol 38, Issue 2, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243802.132
Received: 20 February 2024; Accepted: 20 February 2024; Available online: 20 February 2024; Issue release: 20 February 2024

Abstract

Background: Cerebral ischemic stroke (CIS) results from insufficient blood supply to the brain, leading to disabilities and even death. Currently, available CIS treatment primarily focuses on promoting angiogenesis. The tumor necrosis factor receptor-associated factor 7 (TRAF7) plays a pivotal role in various biological processes and has been associated with neuronal damage. However, its role in CIS remains uncertain. Therefore, this study aimed to investigate the role of TRAF7 in angiogenesis during CIS. Methods: A middle cerebral-arterial occlusion (MCAO) mice model with knocked-down TRAF7 was established to investigate its effects on neurological deficits, brain water content, and infarct volume. CD31/ki67 dual-immunofluorescent (IF) staining was performed to assess the impact of TRAF7 on angiogenesis in vivo. Furthermore, an Oxygen and Glucose Deprivation and Reoxygenation (OGD/R) cell model was constructed to mimic ischemia and explore the influence of the TRAF7/Krupple-like family of transcription factor 4 (KLF4) axis on cell migration and tube formation. Results: TRAF7 protein expression was found to be elevated in both the in vivo and in vitro ischemic models. Its silencing improved neurological function, reduced cerebral water content and infarct volume, and enhanced angiogenesis after CIS in vivo. Furthermore, its silencing promoted bEnd3 cell migration and tube formation following OGD/R injury. Moreover, it was observed that TRAF7 regulated expression levels of KLF4 and vascular endothelial growth factor (VEGF) in both in vivo and in vitro settings. Mechanistically, it was found that TRAF7 mediated bEnd3 cell migration and angiogenesis post-OGD/R injury by modulating KLF4 expression. Conclusions: Our findings indicate that TRAF7 knockdown confers vascular protection against CIS, offering a novel perspective for CIS treatment.


Keywords

cerebral ischemic stroke;angiogenesis;TRAFA7;KLF4;VEGF


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