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Cell and Tissue Research

, Volume 361, Issue 2, pp 497–508 | Cite as

Endoplasmic reticulum stress participates in the progress of senescence of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus

  • Zhifeng Gu
  • Yan Meng
  • Tao Tao
  • Genkai Guo
  • Wei Tan
  • Yunfei Xia
  • Chun ChengEmail author
  • Hong LiuEmail author
Regular Article

Abstract

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.

Keywords

Aging Endoplasmic reticulum stress Mesenchymal stem cells Systemic lupus erythematosus 

Abbreviations

4-PBA

4-phenylbutyric acid

ATF6

Activating transcription factor-6

BM-MSCs

Bone marrow mesenchymal stem cells

BM-MSCT

Bone marrow MSC transplantation

ER

Endoplasmic reticulum

ERS

Endoplasmic reticulum stress

FBS

Fetal bovine serum

FITC

Fluorescein isothiocyanate

GRP 78

Glucose regulated protein 78

IRE-1

Inositol-requiring enzyme 1

L-DMEM

Low-glucose Dulbecco’s Modified Eagle’s Medium

MSCT

Mesenchymal stem cells transplantation

PBS

Phosphate-buffered saline

PERK

Phosphorylated PKR-like ER kinase

PFA

Paraformaldehyde

PVDF

Polyvinylidenedifluoride

SA-β-gal

Senescence-associated β-galactosidase

SLE

Systemic lupus erythematosus

SLEDAI

Systemic lupus erythematosus disease activity index

UPR

Unfolded protein response

Notes

Acknowledgments

This study was supported by grants from the Chinese National Natural Science Foundation (Nos. 81172841 81202368 and 81471603); China Postdoctoral Science Foundation (2013 M541708); the project of “333 Natural Science Foundation” of Jiangsu Grant (BRA2013286); the “Top Six Types of Talents” Financial Assistance of Jiangsu Province Grant (No. 6); the project of Jiangsu Provincial Health Department (Z201005); the innovative project of Nantong University postgraduate students (13025043); and the Jiangsu province’s Outstanding Medical Academic Leader Program (LJ201136).

Conflicts of interest

There are no commercial affiliations or conflict of interests to disclose.

Supplementary material

441_2015_2131_MOESM1_ESM.tif (3.3 mb)
Supplementary figure UPR cause senescence in BM-MSCs from normal patients. Normal cells were treated with 3 μM Tunicamycin (TM) for 24h. ac Tunicamycin increased SA-β-gal-positive cell number. (Bar represents mean ± SD, = 12, *< 0.05 compared with the normal group). d, e The percentage of cells in G1 phase was also increased. (TIFF 3350 kb)
441_2015_2131_Fig5_ESM.gif (1.2 mb)
High Resolution (GIF 1187 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of RheumatologyAffiliated Hospital of Nantong UniversityNantongChina
  2. 2.Department of Immunology, Medical CollegeNantong UniversityNantongChina
  3. 3.Department of HematologyAffiliated Hospital of Nantong UniversityNantongChina

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