Ang1/Tie2/VE-Cadherin Signaling Regulates DPSCs in Vascular Maturation
Ang1/Tie2/VE-Cadherin Signaling Regulates DPSCs in Vascular Maturation
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Ang1/Tie2/VE-钙粘蛋白信号传导调节血管成熟中的 DPSC
DOI：
10.1177/00220345231210227
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发表时间：
2023
影响因子：
7.6
通讯作者：
C. Zhang
中科院分区：
文献类型：
--
作者：
Y. Zhang;S. Lin;J. Liu;Q. Chen;J. Kang;J. Zhong;M. Hu;M. Basabrain;Y. Liang;C. Yuan;C. Zhang
在血管内皮细胞形成的血管样结构中加入牙髓干细胞(DPSCs)可以延长这些血管网络的寿命。DPSCs具有周细胞样细胞功能，可紧密聚集内皮细胞。然而，DPSC来源的周细胞样细胞稳定血管网络的机制还不完全清楚。本研究从人脐静脉内皮细胞与人脐静脉内皮细胞直接共培养中分离出E-DPSCs和经转化生长因子-β-1处理后的T-DPSCs，研究其在体内外稳定血管的作用。采用三维共培养球体萌发实验比较E-DPSCs和T-DPSCs的体外功能。采用严重联合免疫缺陷(SCID)小鼠牙髓血管生成模型，探讨E-DPSCs和T-DPSCs在体内血管形成中的作用。结果表明，E-DPSCs和T-DPSCs均具有平滑肌细胞样细胞特性，表现出较高的壁细胞特异性标志物的表达和抑制HUVEC的萌发。E-DPSCs和T-DPSCs通过激活TEK酪氨酸激酶(Tie2)信号，上调血管内皮细胞(VE)-钙粘附素，下调血管内皮生长因子受体2(VEGFR2)，抑制HUVEC的萌发。体内实验显示，与HUVEC+DPSC组相比，HUVEC+E-DPSC组、HUVEC+T-DPSC组、血管生成素1(Ang1)预处理组和血管内皮细胞酪氨酸磷酸酶(VE-PTP)抑制剂预处理组的血管灌注量和总血管数均明显增加。综上所述，E-DPSCs和T-DPSCs均能稳定新生血管，加速血管灌流。重要的调控途径是Ang1/Tie2/VE-cadherin和VEGF/VEGFR2信号通路。
Adding dental pulp stem cells (DPSCs) to vascular endothelial cell–formed vessel-like structures can increase the longevity of these vessel networks. DPSCs display pericyte-like cell functions and closely assemble endothelial cells (ECs). However, the mechanisms of DPSC-derived pericyte-like cells in stabilizing the vessel networks are not fully understood. In this study, we investigated the functions of E-DPSCs, which were DPSCs isolated from the direct coculture of human umbilical vein endothelial cells (HUVECs) and DPSCs, and T-DPSCs, which were DPSCs treated by transforming growth factor beta 1 (TGF-β1), in stabilizing blood vessels in vitro and in vivo. A 3-dimensional coculture spheroid sprouting assay was conducted to compare the functions of E-DPSCs and T-DPSCs in vitro. Dental pulp angiogenesis in the severe combined immunodeficiency (SCID) mouse model was used to explore the roles of E-DPSCs and T-DPSCs in vascularization in vivo. The results demonstrated that both E-DPSCs and T-DPSCs possess smooth muscle cell–like cell properties, exhibiting higher expression of the mural cell–specific markers and the suppression of HUVEC sprouting. E-DPSCs and T-DPSCs inhibited HUVEC sprouting by activating TEK tyrosine kinase (Tie2) signaling, upregulating vascular endothelial (VE)–cadherin, and downregulating vascular endothelial growth factor receptor 2 (VEGFR2). In vivo study revealed more perfused and total blood vessels in the HUVEC + E-DPSC group, HUVEC + T-DPSC group, angiopoietin 1 (Ang1) pretreated group, and vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibitor pretreated group, compared to HUVEC + DPSC group. In conclusion, these data indicated that E-DPSCs and T-DPSCs could stabilize the newly formed blood vessels and accelerate their perfusion. The critical regulating pathways are Ang1/Tie2/VE-cadherin and VEGF/VEGFR2 signaling.
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影响因子：
15.9
作者：
Shen, Jikui;Frye, Maike;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.
DOI：
10.1089/ten.tec.2011.0744
发表时间：
2012-05
期刊：
Tissue engineering. Part C, Methods
影响因子：
--
作者：
Sean M. White;R. Hingorani;Rajan P S Arora;C. Hughes;S. George;Bernard Choi
通讯作者：
Sean M. White;R. Hingorani;Rajan P S Arora;C. Hughes;S. George;Bernard Choi
影响因子：
11.8
作者：
Gavard, Julie;Patel, Vyomesh;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio
DOI：
10.1016/j.ymthe.2018.03.017
发表时间：
2018-07-05
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
MacAskill MG;Saif J;Condie A;Jansen MA;MacGillivray TJ;Tavares AAS;Fleisinger L;Spencer HL;Besnier M;Martin E;Biglino G;Newby DE;Hadoke PWF;Mountford JC;Emanueli C;Baker AH
通讯作者：
Baker AH
DOI：
10.1073/pnas.240309797
发表时间：
2000-12-05
影响因子：
11.1
作者：
Gronthos, S;Mankani, M;Shi, S
通讯作者：
Shi, S