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Journal of Immunology Research
Volume 2015, Article ID 183738, 13 pages
Research Article

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

1Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China
2Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong 226001, China
3Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226001, China

Received 6 September 2014; Accepted 16 January 2015

Academic Editor: Jianying Zhang

Copyright © 2015 Genkai Guo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.