血管生成
半影
癌症研究
PI3K/AKT/mTOR通路
移植
蛋白激酶B
治疗性血管生成
基因敲除
神经发生
血管内皮生长因子
医学
细胞生物学
新生血管
免疫学
缺血
生物
信号转导
内科学
细胞凋亡
生物化学
血管内皮生长因子受体
作者
Xiaoxiong Zou,Yanyan Xie,Zhongfei Zhang,Zhiming Feng,Jianbang Han,Qian Ouyang,Shiting Hua,Sixian Huang,Cong Liu,Zhizheng Liu,Yuchen Cai,Yong Zou,Yanping Tang,Haijia Chen,Xiaodan Jiang
标识
DOI:10.1016/j.expneurol.2023.114532
摘要
Cerebral ischemia is a serious disease characterized by brain tissue ischemia and hypoxic necrosis caused by the blockage of blood vessels within the central nervous system. Although stem cell therapy is a promising approach for treating ischemic stroke, the inflammatory, oxidative, and hypoxic environment generated by cerebral ischemia greatly reduces the survival and therapeutic effects of transplanted stem cells. Endothelial colony-forming cells (ECFCs) are a class of precursor cells with strong proliferative potential that can migrate and differentiate directly into mature vascular endothelial cells. Consequently, ECFCs can exert significant therapeutic and reparative effects in diseases associated with vascular injury. Monocyte chemoattractant protein-induced protein 1 (MCPIP-1) exerts multiple biological effects; however, no studies have yet reported its role in the angiogenic function of ECFCs. In this study, we performed Proteome Profiler™ Human Angiogenesis Antibody arrays and tandem mass tag protein profiling to investigate the effect of MCPIP-1 on ECFCs. We demonstrated that MCPIP-1 knockdown enhanced the proliferation, migration, and in vivo and in vitro angiogenic capacity of ECFCs by upregulating the transferrin receptor-activated AKT/m-TOR signaling pathway to promote cellular trophic factor secretion. Furthermore, we found that the lateral ventricular transplantation of ECFCs with lentiviral MCPIP-1 knockdown into mice with middle cerebral artery occlusion increased serum vacular endothelial growth factor(VEGF), angiopoietin-1, and HIF-1a levels, enhanced neovascularization and neurogenesis in the ischemic penumbra, reduced the size of cerebral infarcts, and promoted neurological recovery. Together, these findings suggest new avenues for enhancing the therapeutic efficacy of ECFCs.
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