Suppr超能文献

功能性 RIG-I 样受体控制间充质干细胞的存活。

Functional RIG-I-like receptors control the survival of mesenchymal stem cells.

机构信息

1] Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou 510080, China [2] Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.

Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Cell Death Dis. 2013 Dec 12;4(12):e967. doi: 10.1038/cddis.2013.504.

Abstract

Because of their potent regenerative and immunomodulatory properties, mesenchymal stem cells (MSCs) have promising therapeutic benefits in clinical treatment of inflammatory and infectious diseases. Recent studies suggest that many biological activities of MSCs are largely determined by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs). However, the role of PRRs in regulating the survival of MSCs remains unknown. In the present study, we examined the viability of MSCs after stimulation of distinct PRRs. Activation of TLRs by direct addition with their respective ligands showed no significant effect on the survival of MSCs, whereas transfection with double-stranded RNA (dsRNA) resulted in marked cell death in MSCs. Transfection of dsRNA upregulated cytosolic retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated antigen 5 (MDA5). Moreover, transfection of dsRNA activated downstream transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB), as well as induced the expression of interferon-β (IFN-β) and pro-inflammatory cytokine interleukin 6 (IL-6) via RLR signaling. Furthermore, we found that transfection of dsRNA triggered both extrinsic and intrinsic apoptotic responses via RLRs. However, ectopic expression of RIG-I or MDA5 was not sufficient to induce apoptosis of MSCs without dsRNA transfection. Our study also revealed that IκB kinase α/β (IKKα/β) was required for RLR-mediated apoptosis in MSCs, while TANK-binding kinase 1 (TBK1)/IKKɛ served a pro-survival role. Moreover, neither overexpression of B-cell lymphoma 2 (Bcl2) nor neutralizing autocrined IFN-β reduced RLR-mediated apoptosis. In addition, autophagy was induced upon activation of RLRs, however, blocking autophagy did not rescue MSCs from the dsRNA-induced cell death. To the best of our knowledge, this is the first study to explore the role of RLRs in controlling the survival of MSCs, which may provide a clue to understand the pathogenesis of viral infection in MSCs.

摘要

由于间充质干细胞(MSCs)具有强大的再生和免疫调节特性,因此在炎症和感染性疾病的临床治疗中具有有前景的治疗益处。最近的研究表明,MSCs 的许多生物学活性在很大程度上取决于模式识别受体(PRRs),例如 Toll 样受体(TLRs)。然而,PRRs 在调节 MSCs 的存活中的作用尚不清楚。在本研究中,我们检查了不同 PRRs 刺激后 MSCs 的活力。直接用各自的配体激活 TLRs 对 MSCs 的存活没有显著影响,而用双链 RNA(dsRNA)转染则导致 MSCs 明显死亡。dsRNA 的转染上调了细胞质视黄酸诱导基因 I(RIG-I)样受体(RLRs),包括 RIG-I 和黑色素瘤分化相关抗原 5(MDA5)。此外,dsRNA 的转染激活了下游转录因子干扰素调节因子 3(IRF3)和核因子 κB(NF-κB),并通过 RLR 信号诱导干扰素-β(IFN-β)和促炎细胞因子白细胞介素 6(IL-6)的表达。此外,我们发现 dsRNA 通过 RLRs 触发了外在和内在的凋亡反应。然而,没有 dsRNA 转染,RLR 过表达 RIG-I 或 MDA5 不足以诱导 MSCs 凋亡。我们的研究还表明,IκB 激酶 α/β(IKKα/β)是 RLR 介导的 MSCs 凋亡所必需的,而 TANK 结合激酶 1(TBK1)/IKKɛ 则起生存作用。此外,B 细胞淋巴瘤 2(Bcl2)的过表达或中和自分泌 IFN-β 均不能减轻 RLR 介导的凋亡。此外,RLRs 激活后诱导自噬,但阻断自噬并不能挽救 MSCs 免受 dsRNA 诱导的细胞死亡。据我们所知,这是第一项探索 RLRs 在控制 MSCs 存活中的作用的研究,这可能有助于了解 MSCs 中病毒感染的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4be3/3877571/41a69a867165/cddis2013504f1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验