Endoplasmic reticulum stress participates in the progress of senescence of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus
Endoplasmic reticulum stress participates in the progress of senescence of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus
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内质网应激参与系统性红斑狼疮患者骨髓间充质干细胞衰老进程
DOI：
10.1007/s00441-015-2131-x
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发表时间：
2015-08-01
影响因子：
3.6
通讯作者：
Liu, Hong
中科院分区：
文献类型：
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作者：
Gu, Zhifeng;Meng, Yan;Liu, Hong
既往研究表明，骨髓间充质干细胞(BM-MSCs)的衰老在系统性红斑狼疮(SLE)的病理过程中起重要作用。然而，控制这一现象的分子机制还没有完全阐明。最近的研究表明，内质网应激(ERS)的激活参与了细胞周期G1期的生长停滞。本研究旨在探讨ERS是否会诱导SLE患者BM-MSCs的衰老。我们发现SLE患者BM-MSCs中葡萄糖调节蛋白78(GRP 78)的表达增加，提示SLE患者BM-MSCs中ERS的激活。SLE患者的BM-MSCs中也有p27的积聚。有趣的是，作为一种帮助蛋白质正确折叠的化学伴侣，4-苯基丁酸(4-PBA)部分挽救了SLE患者BM-MSCs的衰老，并减轻了p27的水平。这些结果暗示ERS介导的衰老是SLE患者BM-MSCs的关键决定因素。
Previous studies suggested that the senescence of bone marrow mesenchymal stem cells (BM-MSCs) played an important role in the pathological process of systemic lupus erythematosus (SLE). However, the molecular mechanisms that govern this phenomenon have not been fully elucidated. Recent studies reported the activation of endoplasmic reticulum stress (ERS) participated in the growth arrest in G1 phase of cell cycle. In this study, we aimed to investigate whether ERS would induce the senescence of BM-MSCs from SLE patients. We found that there was increased expression of Glucose Regulated Protein 78 (GRP 78) in BM-MSCs from SLE patients, which indicated the activation of ERS in BM-MSCs from SLE patients. Accumulation of p27 was also found in BM-MSCs from SLE patients. Interestingly, as a chemical chaperone helping the correct folding of proteins, 4-phenylbutyric acid (4-PBA) partly rescued the senescence of BM-MSCs from SLE patients and alleviated the level of p27. These results implicated ERS-mediated senescence as a critical determinant of BM-MSCs from SLE patients.