scholarly journals Targeting HMGB1 by ethyl pyruvate ameliorates systemic lupus erythematosus and reverses the senescent phenotype of bone marrow-mesenchymal stem cells

Aging ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 4338-4353 ◽  
Author(s):  
Juan Ji ◽  
Ting Fu ◽  
Chen Dong ◽  
Wenyan Zhu ◽  
Junling Yang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Lupus Erythematosus ◽  
Ethyl Pyruvate ◽  
Systemic Lupus ◽  
Senescent Phenotype ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress through Regulation of CHOP and JNK in Bone Marrow Mesenchymal Stem Cells from Patients with Systemic Lupus Erythematosus

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Genkai Guo ◽  
Yan Meng ◽  
Wei Tan ◽  
Yunfei Xia ◽  
Chun Cheng ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Bone Marrow ◽  
Endoplasmic Reticulum ◽  
Mesenchymal Stem Cells ◽  
Endoplasmic Reticulum Stress ◽  
Lupus Erythematosus ◽  
B Cell Lymphoma ◽  
Systemic Lupus ◽  
Marrow Mesenchymal Stem Cells

Previous studies indicated that bone marrow mesenchymal stem cells (BM-MSCs) from patients with systemic lupus erythematosus (SLE) exhibited the phenomenon of apoptosis. In this study, we aimed to investigate whether apoptosis of BM-MSCs from SLE patients were dysregulated. In this paper, endoplasmic reticulum stress (ERS) was evidenced by increased expression of phosphorylated protein kinase RNA-like ER kinase (PERK) and inositol-requiring protein-1 (IRE-1). We also found the activation of downstream target eukaryotic translation initiator factor 2α(eIF 2α) and CCAAT/enhancer-binding protein- (C/EBP-) homologous protein (CHOP) in BM-MSCs from SLE patients. Interestingly, we discovered that 4-phenylbutyric acid (4-PBA), a selective inhibitor of ERS, blocked the apoptosis of BM-MSCs from SLE patients and alleviated the level of Jun N-terminal kinase1/2 (JNK1/2) and CHOP. Furthermore, blockage of PERK signaling expression by siRNA not only significantly reduced the expression of CHOP, but also activated the anti-apoptotic regulator B-cell lymphoma-2 (Bcl-2). Blockage of IRE-1 or JNK1/2 by siRNA resulted in the decreased expression of JNK1/2 and proapoptosis protein Bcl-2 associated protein X (BAX). These results implicated that ERS-mediated apoptosis was a critical determinant of BM-MSCs from SLE patients.

scholarly journals p53/p21 Pathway Involved in Mediating Cellular Senescence of Bone Marrow-Derived Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Zhifeng Gu ◽  
Jinxia Jiang ◽  
Wei Tan ◽  
Yunfei Xia ◽  
Haixia Cao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Lupus Erythematosus ◽  
Cyclin E ◽  
Cyclin Dependent Kinase ◽  
Systemic Lupus ◽  
Underlying Mechanisms

Our and other groups have found that bone marrow-derived mesenchymal stem cells (BM-MSCs) from systemic lupus erythematosus (SLE) patients exhibited senescent behavior and are involved in the pathogenesis of SLE. Numerous studies have shown that activation of the p53/p21 pathway inhibits the proliferation of BM-MSCs. The aim of this study was to determine whether p53/p21 pathway is involved in regulating the aging of BM-MSCs from SLE patients and the underlying mechanisms. We further confirmed that BM-MSCs from SLE patients showed characteristics of senescence. The expressions of p53 and p21 were significantly increased, whereas levels of Cyclin E, cyclin-dependent kinase-2, and phosphorylation of retinoblastoma protein were decreased in the BM-MSCs from SLE patients and knockdown of p21 expression reversed the senescent features of BM-MSCs from SLE patients. Our results demonstrated that p53/p21 pathway played an important role in the senescence process of BM-MSCs from SLE.

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