FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs

FOXO4 敲低抑制氧化应激诱导的早期促血管生成细胞凋亡，并增强缺血肢体中的新生血管形成能力

• 批准号: 23791509
• 负责人: NAKAYOSHI TAKAHARU
• 金额: $ 2.66万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791509/
• 关键词: 前血管新生細胞; アポトーシス; 酸化ストレス; FOXO; 血管新生療法; 血管内皮前駆細胞; 重症虚血肢

We assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs.We transfected small interfering RNA (siRNA) targeted against FOXO4 to EPCs cultured from human peripheral mononuclear cells. In western blotting analyses, FOXO4 siRNA-transfected EPCs (FOXO4 KD -EPCs) showed 45% knockdown of FOXO4 and decreased expressions of pro-apoptotic proteins such as Bim and cleaved caspase-3. The FOXO4 knockdown significantly reduced the percentage of TUNEL-positive apoptotic EPCs induced by H2O2 in the flow cytometry analysis. Intramuscular injection of FOXO4 KD -EPCs to hind-limb ischemia rats significantly increased ischemic/non-ischemic hind-limb blood flow ratio and capillary density of the ischemic adductor muscle after 4 days compared to the injection of Nega-EPCs. FOXO4 KD -EPCs showed anti-apoptosis capacity, which may have contributed to neovascularization in ischemic tissues.

为探讨FOXO 4基因敲减的EPCs（FOXO 4KD-EPCs）是否能抑制氧化应激诱导的细胞凋亡，增强缺血肢体血管新生能力，我们将FOXO 4基因的小干扰RNA（siRNA）转染人外周血单个核细胞培养的EPCs。在蛋白质印迹分析中，FOXO 4 siRNA转染的EPCs（FOXO 4 KD -EPCs）显示FOXO 4敲低45%，促凋亡蛋白如Bim和裂解的caspase-3的表达降低。在流式细胞仪分析中，FOXO 4敲低显著降低了H2 O2诱导的TUNEL阳性凋亡EPCs的百分比。与注射Nega-EPCs相比，向后肢缺血大鼠肌内注射FOXO 4 KD-EPCs 4天后显著增加缺血/非缺血后肢血流比率和缺血收肌的毛细血管密度。FOXO 4 KD-EPCs具有抗凋亡的能力，这可能有助于缺血组织中的新生血管形成。

项目成果

FOXO4-knockdown Augmented Anti-apoptosis and Neovascularization Capacities of Atherosclerotic Patient-derived Circulating Angiogenic Cells

FOXO4 敲低增强动脉粥样硬化患者来源的循环血管生成细胞的抗凋亡和新血管形成能力

• 发表时间: 2013
• 作者: Nakayoshi T,Sasaki K,Ueno T,Kajimoto H,Yokoyama S,Ohtsuka M,Koiwaya H;Itaya N,Tibana H,Imaizumi T
• 通讯作者: Itaya N,Tibana H,Imaizumi T

FOXO4-knockdown Augments Anti-apoptosis and Neovascularization Capacities of Human Early Endothelial Progenitors Cells

FOXO4 敲低增强人早期内皮祖细胞的抗凋亡和新血管形成能力

• 发表时间: 2013
• 作者: 仲吉孝晴;佐々木健一郎;上野高史;梶本英美;横山晋二;大塚昌紀;小岩屋宏;板家直樹;知花英俊;今泉勉
• 通讯作者: 今泉勉

Augmented neovascularization capacities of endothelial progenitor cells via anti-apoptotic effect by FOXO4 siRNA transfection in rats

FOXO4 siRNA转染大鼠体内通过抗凋亡作用增强内皮祖细胞的新生血管能力

• 发表时间: 2013
• 作者: Nakayoshi T,Sasaki K,Ueno T,Kajimoto H,Yokoyama S,Ohtsuka M,Koiwaya H;Itaya N,Tibana H,Imaizumi T;Takaharu Nakayoshi;Takaharu Nakayoshi
• 通讯作者: Takaharu Nakayoshi

FOXO4-knockdown augmented anti-apoptosis and neovascularization capacities of human early pro-angiogenic cells in rat ischemic limbs

FOXO4敲低增强了大鼠缺血肢体中人类早期促血管生成细胞的抗凋亡和新血管形成能力

• 发表时间: 2014
• 作者: Takaharu Nakayoshi^1;Ken-ichiro Sasaki^1;Tsutomu Imaizumi^2;Takafumi Ueno^1;Hidemi Kajimoto^3;Hiroki Aoki^3;Shinji Yokoyama^1;Yasuyuki Toyama^1;Hiroshi Koiwaya^1;Masanori Ohtsuka^1;Yoshiaki Mitsutake^1;Naoki Itaya^1;Hidetoshi Chibana^1;and Yo
• 通讯作者: and Yo

Augmented Neovascularization Capacities of Endothelial Progenitor Cells via Anti-Apoptotic Effect by FOXO4 siRNA Transfection in Rats

FOXO4 siRNA 转染大鼠体内通过抗凋亡作用增强内皮祖细胞的新血管形成能力

• 发表时间: 2014
• 作者: 仲吉孝晴;佐々木健一郎;上野高史;梶本英美;横山晋二;大塚昌紀;小岩屋宏;板家直樹;知花英俊;佐々木雅浩;今泉勉;福本義弘;Takaharu Nakayoshi
• 通讯作者: Takaharu Nakayoshi