G-CSF protects human brain vascular endothelial cells injury induced by high glucose, free fatty acids and hypoxia through MAPK and Akt signaling.
G-CSF protects human brain vascular endothelial cells injury induced by high glucose, free fatty acids and hypoxia through MAPK and Akt signaling.
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G-CSF 通过 MAPK 和 Akt 信号传导保护高血糖、游离脂肪酸和缺氧引起的人脑血管内皮细胞损伤
DOI：
10.1371/journal.pone.0120707
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hu R
中科院分区：
文献类型：
--
作者：
Su J;Zhou H;Tao Y;Guo J;Guo Z;Zhang S;Zhang Y;Huang Y;Tang Y;Dong Q;Hu R
粒细胞集落刺激因子（G-CSF）通过动员骨髓来源的内皮祖细胞（EPCs）、促进血管生成和抑制细胞凋亡，在缺血性卒中中发挥神经保护作用。先前在糖尿病的动物和人类研究中已经报道了BM衍生的EPCs的动员和功能的损伤，其中存在BM衍生的EPCs的水平和其促进血管生成的能力的降低。这被假设为糖尿病血管并发症如中风的发病机制。在这里，我们试图研究G-CSF对糖尿病相关脑血管缺损的影响。我们观察到，用G-CSF预处理培养的人脑血管内皮细胞（HBVECs），通过增加细胞活力、降低凋亡和caspase-3活性，在很大程度上防止了高糖、游离脂肪酸（FFA）和缺氧联合刺激诱导的细胞死亡。透射电子显微镜（TEM）显示，G-CSF处理很好地减少了联合刺激诱导的细胞凋亡的细胞超微结构。荧光探针Fluo-3/AM的结果表明，G-CSF对联合刺激下细胞内钙离子浓度的变化有明显的抑制作用。我们还发现，G-CSF增强细胞周期蛋白，如人细胞分裂周期蛋白14 A（hCdc 14 A），cyclinB和cyclinE的表达，抑制p53活性，并促进细胞周期的进展后，联合刺激。此外，细胞外信号调节激酶1/2（ERK 1/2）和Akt的激活以及c-Jun N末端激酶（JNK）和p38的失活被证明是G-CSF对暴露于组合刺激的HBVECs的促存活效应所必需的。总体而言，G-CSF能够减轻由高糖、FFA和缺氧联合给药引发的涉及丝裂原活化蛋白激酶（MAPK）和Akt信号级联的HBVEC损伤。G-CSF可能是治疗糖尿病性脑卒中的一种有前途的药物。
Granulocyte-colony stimulating factor (G-CSF) has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA) and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM) revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c-Jun N terminal kinase (JNK) and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK) and Akt signaling cascades. G-CSF may represent a promising therapeutic agent for diabetic stroke.
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DOI：
10.1186/alzrt67
发表时间：
2011-03-15
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Li B;Gonzalez-Toledo ME;Piao CS;Gu A;Kelley RE;Zhao LR
通讯作者：
Zhao LR
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
3.7
作者：
Floel A;Warnecke T;Duning T;Lating Y;Uhlenbrock J;Schneider A;Vogt G;Laage R;Koch W;Knecht S;Schäbitz WR
通讯作者：
Schäbitz WR
影响因子：
4.4
作者：
Okazaki, T;Ebihara, S;Yamaya, M
通讯作者：
Yamaya, M
G-CSF 和神经保护：脑缺血的治疗视角。
影响因子：
3.9
作者：
Lu, C. -Z.;Xiao, B. -G.
通讯作者：
Xiao, B. -G.