Hyperactive RAS/PI3-K/MAPK Signaling Cascade in Migration and Adhesion of Nf1 Haploinsufficient Mesenchymal Stem/Progenitor Cells.
Hyperactive RAS/PI3-K/MAPK Signaling Cascade in Migration and Adhesion of Nf1 Haploinsufficient Mesenchymal Stem/Progenitor Cells.
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Nf1 单倍体不足间充质干细胞/祖细胞迁移和粘附中过度活跃的 RAS/PI3-K/MAPK 信号级联
DOI：
10.3390/ijms160612345
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发表时间：
2015-06-01
影响因子：
5.6
通讯作者：
Yang FC
中科院分区：
文献类型：
--
作者：
Zhou Y;He Y;Sharma R;Xing W;Estwick SA;Wu X;Rhodes SD;Xu M;Yang FC
1 型神经纤维瘤病 (NF1) 是一种由 NF1 肿瘤抑制基因突变引起的常染色体显性遗传疾病，影响大约三千分之一的个体。 NF1 患者患有一系列恶性和非恶性表现，例如丛状神经纤维瘤和骨骼异常。我们之前证明，间充质干细胞/祖细胞（MSPC）中的 Nf1 单倍体不足会导致成骨细胞分化受损，这可能与 NF1 患者的骨骼表现有关。在这里，我们试图进一步确定 Nf1 在调节 Nf1 单倍体不足 (Nf1+/-) 小鼠 MSPC 迁移和粘附中的作用。与野生型 (WT) MSPC 相比，Nf1+/- MSPC 表现出核质比增加、迁移增加和肌动蛋白聚合增加。此外，Nf1+/- MSPC 显着增强了细胞对纤连蛋白的粘附，对 CH271 具有选择性亲和力，并过度表达其互补受体 CD49e。与 WT MSPC 相比，Nf1+/- MSPC 还表现出磷酸肌醇 3 激酶 (PI3-K) 和丝裂原激活蛋白激酶 (MAPK) 信号通路的过度激活，在存在药物抑制剂 LY294002 和 PD0325901 的情况下，这些信号通路均显着降低。总的来说，我们的研究表明 PI3-K 和 MAPK 信号通路在增强 Nf1 单倍体 MSPC 的迁移和粘附方面发挥着重要作用。
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by mutations in the NF1 tumor suppressor gene, which affect approximately 1 out of 3000 individuals. Patients with NF1 suffer from a range of malignant and nonmalignant manifestations such as plexiform neurofibromas and skeletal abnormalities. We previously demonstrated that Nf1 haploinsufficiency in mesenchymal stem/progenitor cells (MSPCs) results in impaired osteoblastic differentiation, which may be associated with the skeletal manifestations in NF1 patients. Here we sought to further ascertain the role of Nf1 in modulating the migration and adhesion of MSPCs of the Nf1 haploinsufficient (Nf1+/−) mice. Nf1+/− MSPCs demonstrated increased nuclear-cytoplasmic ratio, increased migration, and increased actin polymerization as compared to wild-type (WT) MSPCs. Additionally, Nf1+/− MSPCs were noted to have significantly enhanced cell adhesion to fibronectin with selective affinity for CH271 with an overexpression of its complimentary receptor, CD49e. Nf1+/− MSPCs also showed hyperactivation of phosphoinositide 3-kinase (PI3-K) and mitogen activated protein kinase (MAPK) signaling pathways when compared to WT MSPCs, which were both significantly reduced in the presence of their pharmacologic inhibitors, LY294002 and PD0325901, respectively. Collectively, our study suggests that both PI3-K and MAPK signaling pathways play a significant role in enhanced migration and adhesion of Nf1 haploinsufficient MSPCs.
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血管内皮生长因子可以通过血小板衍生的生长因子受体发出信号。
影响因子：
7.8
作者：
Ball, Stephen G;Shuttleworth, C Adrian;Kielty, Cay M
通讯作者：
Kielty, Cay M
DOI：
10.1186/1478-811x-3-2
发表时间：
2005-01-31
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Kingsley K;Plopper GE
通讯作者：
Plopper GE
影响因子：
5.2
作者：
Lopez Ponte, Adriana;Marais, Emeline;Domenech, Jorge
通讯作者：
Domenech, Jorge
影响因子：
4
作者：
Illés, T;Halmai, V;Dubousset, J
通讯作者：
Dubousset, J
影响因子：
6.5
作者：
Meirelles, LD;Nardi, NB
通讯作者：
Nardi, NB