Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells.
Modulation of cellular stress response via the erythropoietin/CD131 heteroreceptor complex in mouse mesenchymal-derived cells.
复制标题
通过小鼠间充质衍生的细胞中的红细胞生成素/CD131杂音复合物对细胞应激反应的调节。
DOI：
10.1007/s00109-014-1218-2
复制
发表时间：
2015-02
影响因子：
4.7
通讯作者：
Yarmush, Martin L.
中科院分区：
文献类型：
--
作者：
Bohr, Stefan;Patel, Suraj J.;Vasko, Radovan;Shen, Keyue;Iracheta-Vellve, Arvin;Lee, Jungwoo;Bale, Shyam Sundhar;Chakraborty, Nilay;Brines, Michael;Cerami, Anthony;Berthiaume, Francois;Yarmush, Martin L.
促红细胞生成素（EPO）的组织保护特性使得通过EPO- r /CD131受体复合物的替代EPO信号传导的发现，现在可以通过药物设计的短序列肽（如ARA290）特异性靶向。然而，关于epo信号在特定细胞群中的特定功能，我们所知甚少。在这项研究中，我们研究了通过EPO-R/CD131复合物的信号传导对不同间质来源表型的细胞应激反应和促炎激活的影响。我们发现，ARA290和EPO的抗凋亡、抗炎作用与CD131受体成分的外化一致，作为细胞应激的直接反应。此外，在应激源去除后，可选择的epo信号强烈调节转录、翻译或代谢反应。具体来说，我们发现ARA290能够克服tnf α介导的与细胞应激反应相关的转录因子激活抑制，最明显的是血清反应因子（SRF）、热休克转录因子蛋白1 （HSF1）和激活蛋白1 （AP1）。我们得出结论，epo信号作为促炎信号通路的调节剂，可能在恢复组织稳态中发挥作用。
Tissue protective properties of erythropoietin (EPO) have let to the discovery of an alternative EPO-signaling via an EPO-R/CD131 receptor complex which can now be specifically targeted through pharmaceutically designed short sequence peptides such as ARA290. However, little is still known about specific functions of alternative EPO-signaling in defined cell populations. In this study we investigated effects of signaling through EPO-R/CD131 complex on cellular stress responses and pro-inflammatory activation in different mesenchymal-derived phenotypes. We show that anti-apoptotic, anti-inflammatory effects of ARA290 and EPO coincide with the externalization of CD131 receptor component as an immediate response to cellular stress. In addition, alternative EPO-signaling strongly modulated transcriptional, translational or metabolic responses after stressor removal. Specifically, we saw that ARA290 was able overcome a TNFα-mediated inhibition of transcription factor activation related to cell stress responses, most notably of serum response factor (SRF), heat shock transcription factor protein 1 (HSF1) and activator protein 1 (AP1). We conclude that alternative EPO-signaling acts as a modulator of pro-inflammatory signaling pathways and likely plays a role in restoring tissue homeostasis.
登录
查看更多内容
影响因子：
4.4
作者：
Chandel, NS;Trzyna, WC;Schumacker, PT
通讯作者：
Schumacker, PT
DOI：
10.1073/pnas.1214099110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Bohr, Stefan;Patel, Suraj J.;Yarmush, Martin L.
通讯作者：
Yarmush, Martin L.
影响因子：
3.8
作者：
Su, Xin;Sykes, Joshua B.;Ao, Lihua;Raeburn, Christopher D.;Fullerton, David A.;Meng, Xianzhong
通讯作者：
Meng, Xianzhong
影响因子：
3.2
作者：
Hamid, R;Rotshteyn, Y;Bullock, P
通讯作者：
Bullock, P
DOI：
10.2741/1240
发表时间：
2004-01-01
期刊：
FRONTIERS IN BIOSCIENCE
影响因子：
--
作者：
Fitzgerald, SM;Chi, DS;Krishnaswamy, G
通讯作者：
Krishnaswamy, G