bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways.

bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways.
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DOI:
10.7150/ijbs.11921
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发表时间:
2015
影响因子:
9.2
通讯作者:
Xiao J
Xiao J
中科院分区:
生物学2区
文献类型:
--
作者:
Shi H;Cheng Y;Ye J;Cai P;Zhang J;Li R;Yang Y;Wang Z;Zhang H;Lin C;Lu X;Jiang L;Hu A;Zhu X;Zeng Q;Fu X;Li X;Xiao J

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成纤维细胞在皮肤创伤修复过程中起着关键作用,而它们在糖尿病条件下的迁移能力显著降低。在这项研究中,我们研究了碱性成纤维细胞生长因子(bFGF)在高糖环境中对人真皮成纤维细胞迁移的影响。bFGF通过增加具有高极性指数的成纤维细胞的百分比和重组F-肌动蛋白来显著增加真皮成纤维细胞迁移。在糖尿病条件下bFGF治疗后,在真皮成纤维细胞中观察到细胞内活性氧(ROS)的显着增加。通过ROS清除剂N-乙酰-L-半胱氨酸(NAC)或NADPH氧化酶抑制剂氯化二苯碘鎓(DPI)阻断bFGF诱导的ROS产生几乎完全中和了bFGF促进的真皮成纤维细胞迁移率增加。Akt、Rac 1和JNK在真皮成纤维细胞中被bFGF迅速激活,bFGF诱导的ROS产生和促进的真皮成纤维细胞迁移在分别被抑制时显著减弱。此外,bFGF诱导的ROS产生的增加是必不可少的激活粘着斑激酶(FAK)和桩蛋白。因此,我们的数据表明,碱性成纤维细胞生长因子促进迁移的人皮肤成纤维细胞在糖尿病条件下,通过增加活性氧的生产,通过PI 3 K/Akt-Rac 1-JNK途径。
Fibroblasts play a pivotal role in the process of cutaneous wound repair, whereas their migratory ability under diabetic conditions is markedly reduced. In this study, we investigated the effect of basic fibroblast growth factor (bFGF) on human dermal fibroblast migration in a high-glucose environment. bFGF significantly increased dermal fibroblast migration by increasing the percentage of fibroblasts with a high polarity index and reorganizing F-actin. A significant increase in intracellular reactive oxygen species (ROS) was observed in dermal fibroblasts under diabetic conditions following bFGF treatment. The blockage of bFGF-induced ROS production by either the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) almost completely neutralized the increased migration rate of dermal fibroblasts promoted by bFGF. Akt, Rac1 and JNK were rapidly activated by bFGF in dermal fibroblasts, and bFGF-induced ROS production and promoted dermal fibroblast migration were significantly attenuated when suppressed respectively. In addition, bFGF-induced increase in ROS production was indispensable for the activation of focal adhesion kinase (FAK) and paxillin. Therefore, our data suggested that bFGF promotes the migration of human dermal fibroblasts under diabetic conditions through increased ROS production via the PI3K/Akt-Rac1-JNK pathways.
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