SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis.
SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis.
复制标题
SMAD 特异性 E3 泛素连接酶 2 通过促进强直性脊柱炎患者 MSC 中 PTX3 降解来促进血管生成
DOI：
10.1002/stem.3332
复制
发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Ma M;Yang W;Cai Z;Wang P;Li H;Mi R;Jiang Y;Xie Z;Sui P;Wu Y;Shen H
间充质干细胞（MSCs）血管生成失调与各种自身免疫性疾病患者的炎症和骨代谢紊乱密切相关。然而，骨髓间充质干细胞在强直性脊柱炎（AS）患者异常血管生成中的作用仍不清楚。在这项研究中，我们在体外培养人脐静脉内皮细胞（HUVECs）与来自AS患者（ASMSCs）或健康供体（HDMSCs）的骨髓源性MSCs。然后，使用细胞计数试剂盒-8（CCK-8）测定共培养的HUVEC以评价细胞增殖。进行伤口愈合测定以研究细胞迁移，并进行管形成测定以确定血管生成效率。ASMSC表现出血管生成增加，而MSC中SMAD特异性E3遍在蛋白连接酶2（Smurf 2）表达增加是AS患者血管生成异常的主要原因。Smurf 2在ASMSC中的下调阻断了血管生成，而Smurf 2在HDMSC中的过表达促进了血管生成。体内基质胶塞测定的结果证实了Smurf 2的促血管生成作用。通过在MSC中作为E3泛素连接酶发挥作用，Smurf 2调节五聚蛋白3（PTX 3）的水平，PTX 3已被证明通过PTX 3-成纤维细胞生长因子2途径抑制血管生成。此外，Smurf 2的转录受激活转录因子4诱导的内质网应激的调节。总之，这些结果确定了Smurf 2在ASMSC中负调节PTX 3稳定性和促进血管生成的新作用。SMAD特异性E3泛素蛋白连接酶2（Smurf 2）转录受激活转录因子4诱导的内质网应激调控，Smurf 2负调控强直性脊柱炎间充质干细胞中五聚蛋白3（PTX 3）的稳定性，并通过PTX 3-成纤维细胞生长因子2轴异常促进血管生成。
Dysregulated angiogenesis of mesenchymal stem cells (MSCs) is closely related to inflammation and disrupted bone metabolism in patients with various autoimmune diseases. However, the role of MSCs in the development of abnormal angiogenesis in patients with ankylosing spondylitis (AS) remains unclear. In this study, we cultured human umbilical vein endothelial cells (HUVECs) with bone marrow‐derived MSCs from patients with AS (ASMSCs) or healthy donors (HDMSCs) in vitro. Then, the cocultured HUVECs were assayed using a cell counting kit‐8 (CCK‐8) to evaluate the cell proliferation. A wound healing assay was performed to investigate cell migration, and a tube formation assay was conducted to determine the angiogenesis efficiency. ASMSCs exhibited increased angiogenesis, and increased expression of SMAD‐specific E3 ubiquitin ligase 2 (Smurf2) in MSCs was the main cause of abnormal angiogenesis in patients with AS. Downregulation of Smurf2 in ASMSCs blocked angiogenesis, whereas overexpression of Smurf2 in HDMSCs promoted angiogenesis. The pro‐angiogenic effect of Smurf2 was confirmed by the results of a Matrigel plug assay in vivo. By functioning as an E3 ubiquitin ligase in MSCs, Smurf2 regulated the levels of pentraxin 3 (PTX3), which has been shown to suppress angiogenesis through the PTX3‐fibroblast growth factor 2 pathway. Moreover, Smurf2 transcription was regulated by activating transcription factor 4‐induced endoplasmic reticulum stress. In conclusion, these results identify novel roles of Smurf2 in negatively regulating PTX3 stability and promoting angiogenesis in ASMSCs. SMAD‐specific E3 ubiquitin protein ligase 2 (Smurf2) transcription is regulated by activating transcription factor 4‐induced endoplasmic reticulum stress, and Smurf2 negatively regulates pentraxin 3 (PTX3) stability in ankylosing spondylitis mesenchymal stem cells and abnormally promotes angiogenesis through the PTX3‐fibroblast growth factor 2 axis.
登录
查看更多内容
影响因子：
3.3
作者：
Cao S;Xiao L;Rao JN;Zou T;Liu L;Zhang D;Turner DJ;Gorospe M;Wang JY
通讯作者：
Wang JY
从间充质干细胞释放的肝素酶激活整联蛋白beta1/hif-2alpha/flk-1信号传导，并促进内皮细胞迁移和血管生成。
影响因子：
5.2
作者：
Hu, Xinyang;Zhang, Ling;Jin, Jing;Zhu, Wei;Xu, Yinchuan;Wu, Yan;Wang, Yingchao;Chen, Han;Webster, Keith A.;Chen, Huiqiang;Yu, Hong;Wang, Jian'an
通讯作者：
Wang, Jian'an
影响因子：
8
作者：
Manikoth Ayyathan, Dhanoop;Koganti, Praveen;Blank, Michael
通讯作者：
Blank, Michael
影响因子：
4.7
作者：
Koganti P;Levy-Cohen G;Blank M
通讯作者：
Blank M
内皮和间质干细胞的血管生成和免疫调节特性。
影响因子：
--
作者：
Bartaula-Brevik S;Pedersen TO;Finne-Wistrand A;Bolstad AI;Mustafa K
通讯作者：
Mustafa K