SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways.
SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways.
复制标题
SDF-1/CXCR4 轴通过 FAK/PI3K/Akt 和 GSK3beta/beta-catenin 途径诱导人牙髓干细胞迁移。
DOI：
10.1038/srep40161
复制
发表时间：
2017-01-09
影响因子：
4.6
通讯作者：
Yu Q
中科院分区：
文献类型：
--
作者：
Li M;Sun X;Ma L;Jin L;Zhang W;Xiao M;Yu Q
已发现SDF-1（基质细胞衍生因子-1）在牙髓炎症过程中广泛表达，而hDPSC（人牙髓干细胞）有助于牙髓的修复。我们发现SDF-1以浓度依赖性方式诱导hDPSCs迁移，并且可以被siCXCR 4（C-X-C趋化因子受体4型）和siCDC 42（细胞分裂控制蛋白42）以及药物抑制剂如AMD 3100（CXCR 4拮抗剂）、LY 294002（PI 3 K抑制剂）和PF 573228（FAK抑制剂）抑制。SDF-1还可调节细胞膜FAK（focal adhesion kinases）的磷酸化和β-catenin向细胞核的转位。随后的实验证实，CXCR 4和β-catenin的表达以及FAK、PI 3 K（磷酸肌醇3-激酶）、Akt和GSK 3 β（糖原合成酶激酶-3 β）的磷酸化在SDF-1刺激下显著改变。FAK和PI 3 K在此过程中进行了协调。我们的研究结果为SDF-1/CXCR 4轴通过FAK/PI 3 K/Akt和GSK 3 β/β-catenin途径诱导hDPSCs迁移提供了直接证据，暗示了一种新的牙髓修复机制以及SDF-1在牙髓炎治疗中的可能应用。
SDF-1 (stromal cell derived factor-1) has been found to be widely expressed during dental pulp inflammation, while hDPSCs (human dental pulp stem cells) contribute to the repair of dental pulp. We showed that the migration of hDPSCs was induced by SDF-1 in a concentration-dependent manner and could be inhibited with siCXCR4 (C-X-C chemokine receptor type 4) and siCDC42 (cell division control protein 42), as well as drug inhibitors such as AMD3100 (antagonist of CXCR4), LY294002 (inhibitor of PI3K) and PF573228 (inhibitor of FAK). It was also confirmed that SDF-1 regulated the phosphorylation of FAK (focal adhesion kinases) on cell membranes and the translocation of β-catenin into the cell nucleus. Subsequent experiments confirmed that the expression of CXCR4 and β-catenin and the phosphorylation of FAK, PI3K (phosphoinositide 3-kinase), Akt and GSK3β (glycogen synthase kinase-3β) were altered significantly with SDF-1 stimulation. FAK and PI3K worked in coordination during this process. Our findings provide direct evidence that SDF-1/CXCR4 axis induces hDPSCs migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways, implicating a novel mechanism of dental pulp repair and a possible application of SDF-1 for the treatment of pulpitis.
登录
查看更多内容
影响因子：
20.3
作者：
Cho, Byung-Sik;Zeng, Zhihong;Konopleva, Marina
通讯作者：
Konopleva, Marina
影响因子：
2.2
作者：
Hu, Changjiang;Yong, Xin;Liang, Guangping
通讯作者：
Liang, Guangping
DOI：
10.1073/pnas.102657399
发表时间：
2002-05-14
影响因子：
11.1
作者：
Cheon, SS;Cheah, AYL;Alman, BA
通讯作者：
Alman, BA
影响因子：
64.8
作者：
Clark, EA;Golub, TR;Hynes, RO
通讯作者：
Hynes, RO
基质细胞衍生的 Factor-1/CXCR4 信号传导在体外改变人胚胎干细胞衍生的内皮细胞的毛细血管样组织
影响因子：
5.2
作者：
Chen, Tong;Bai, Hao;Wang, Zack Z.
通讯作者：
Wang, Zack Z.