Sema4D/PlexinB1 promotes endothelial differentiation of dental pulp stem cells via activation of AKT and ERK1/2 signaling

Sema4D/PlexinB1 promotes endothelial differentiation of dental pulp stem cells via activation of AKT and ERK1/2 signaling
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Sema4D/PlexinB1 通过激活 AKT 和 ERK1/2 信号促进牙髓干细胞的内皮分化

DOI:
10.1002/jcb.28635
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发表时间:
2019-08
影响因子:
4
通讯作者:
Zhang Chengfei
Zhang Chengfei
中科院分区:
生物学2区
文献类型:
--
作者:
Zou Ting;Jiang Shan;Dissanayaka Waruna Lakmal;Heng Boon Chin;Xu Jianguang;Gong Ting;Huang Xiaojing;Zhang Chengfei

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将牙髓干细胞(DPSC)诱导为内皮细胞(EC),使牙髓组织预血管化,可能为促进牙髓再生提供一种新的可行方法。然而,在用于获取足够的翻译EC的当前方法中存在许多挑战。Sema 4D/PlexinB 1信号通路在促进血管内皮生长因子(VEGF)分泌和血管生成中发挥重要作用。Sema 4D/PlexinB 1是否能调控DPSCs的内皮分化尚不清楚。在这项研究中,当DPSC用Sema 4D(2 μg/mL)处理时,EC特异性(VEGFR 1,VEGFR 2,CD 31和vWF)以及血管生成基因和蛋白质显著上调。诱导后的内皮细胞具有与人脐静脉内皮细胞(HUVECs)相似的内皮血管形成能力。此外,AKT的磷酸化在5分钟内急剧增加(从0.93增加到21.8),而p-ERK 1/2中度升高(从0.94增加到2.65)。总之,我们的结果表明,Sema 4D/丛蛋白B1信号诱导DPSC的内皮分化。Sema 4D、VEGF、ANGPTL 4、ANG 1和HIF-1α的相互作用可能在介导分化过程中起关键作用。
Inducing of dental pulp stem cells (DPSCs) into endothelial cells (ECs) to prevascularize pulp tissue constructs may offer a novel and viable approach for enhancing pulp regeneration. However, there are numerous challenges in current methods for the acquisition of sufficient translational ECs. It was known that Sema4D/PlexinB1 signaling exerts profound effects on enhancing vascular endothelial growth factor (VEGF) secretion and angiogenesis. Whether Sema4D/PlexinB1 could regulate endothelial differentiation of DPSCs is not yet investigated. In this study, when DPSCs were treated with Sema4D (2 μg/mL), ECs‐specific (VEGFR1, VEGFR2, CD31, and vWF), and angiogenic genes and proteins were significantly upregulated. The induced ECs exhibited similar endothelial vessel formation ability to that of human umbilical vein endothelial cells (HUVECs). Furthermore, phosphorylation of AKT increased dramatically within 5 minutes (from 0.93 to 21.8), while p‐ERK1/2 was moderately elevated (from 0.94 to 2.65). In summary, our results demonstrated that Sema4D/PlexinB1 signaling induces endothelial differentiation of DPSCs. The interactions of Sema4D, VEGF, ANGPTL4, ANG1, and HIF‐1α may play a crucial role in mediating the differentiation process.
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