Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients.
Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients.
复制标题
TRAF4 表达升高会损害强直性脊柱炎患者间充质干细胞中 LPS 诱导的自噬。
DOI：
10.1038/emm.2017.69
复制
发表时间：
2017-06-09
影响因子：
12.8
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Li J;Wang P;Xie Z;Yang R;Li Y;Wu X;Su H;Deng W;Wang S;Liu Z;Cen S;Ouyang Y;Wu Y;Shen H
强直性脊柱炎（AS）是一种自身免疫性疾病，主要影响脊柱和骶髂关节。然而，AS的发病机制尚不清楚。一些证据表明，细菌感染，特别是革兰氏阴性菌感染，可能在AS的发生和发展中起重要作用。近年来，许多研究表明，间充质干细胞（MSCs）功能障碍可能与许多风湿性疾病的发病机制有关。我们之前已经证明，在非炎症条件下，来自AS患者的MSCs在体外表现出明显增强的成骨分化能力。然而，炎性环境下AS患者骨髓间充质干细胞的特性从未被研究过。脂多糖（LPS）是一种源自革兰氏阴性菌外膜的促炎物质，可以改变间充质干细胞的状态和功能。然而，AS患者的MSCs是否对LPS刺激表现出异常反应尚未见报道。自噬是溶酶体介导的分解代谢过程，参与许多生理和病理过程。自噬和AS之间的联系在很大程度上仍然未知。LPS刺激后ASMSCs的自噬水平仍有待研究。在这项研究中，我们证明了尽管健康供体间充质干细胞（HDMSCs）和ASMSCs的自噬基础水平没有差异，但lps诱导的ASMSCs的自噬比HDMSCs弱。具体来说，ASMSCs中TRAF4表达的增加可能通过抑制Beclin-1的磷酸化而损害了lps诱导的自噬。这些数据可能为ASMSC功能障碍和AS发病的确切机制提供进一步的见解。
Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions. However, the properties of MSCs from AS patients in an inflammatory environment have never been explored. Lipopolysaccharide (LPS), a proinflammatory substance derived from the outer membrane of Gram-negative bacteria, can alter the status and function of MSCs. However, whether MSCs from AS patients exhibit abnormal responses to LPS stimulation has not been reported. Autophagy is a lysosome-mediated catabolic process that participates in many physiological and pathological processes. The link between autophagy and AS remains largely unknown. The level of autophagy in ASMSCs after LPS stimulation remains to be addressed. In this study, we demonstrated that although the basal level of autophagy did not differ between MSCs from healthy donors (HDMSCs) and ASMSCs, LPS-induced autophagy was weaker in ASMSCs than in HDMSCs. Specifically, increased TRAF4 expression in ASMSCs impaired LPS-induced autophagy, potentially by inhibiting the phosphorylation of Beclin-1. These data may provide further insight into ASMSC dysfunction and the precise mechanism underlying the pathogenesis of AS.
登录
查看更多内容
影响因子：
27.4
作者：
Ciccia F;Accardo-Palumbo A;Rizzo A;Guggino G;Raimondo S;Giardina A;Cannizzaro A;Colbert RA;Alessandro R;Triolo G
通讯作者：
Triolo G
影响因子：
3.7
作者：
Hwang SH;Cho HK;Park SH;Lee W;Lee HJ;Lee DC;Oh JH;Park SH;Kim TG;Sohn HJ;Kang JM;Kim SW
通讯作者：
Kim SW
影响因子：
--
作者：
Davidson, Stuart I.;Wu, Xin;Xu, Huji
通讯作者：
Xu, Huji
自噬通过减少间充质干细胞中ROS的产生来防止辐射损伤并保持干性
影响因子：
9
作者：
通讯作者：
--
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF