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Wnt/β-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway

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Abstract

Recent studies have shown that allogeneic bone marrow (BM)-mesenchymal stem cell transplantation (MSCT) appears to be effective in systemic lupus erythematosus (SLE) patients and lupus-prone mice, contrary to studies in syngeneic BM-MSCT. These studies indicated that the abnormalities of BM-MSCs may be involved in the pathogenesis of SLE. Our studies and other previous studies have revealed that BM-MSCs from SLE patients exhibited early signs of senescence, such as flattened morphology, slow proliferation, increased senescence-associated β-galactosidase (SA-β-gal) activity, and so on. However, the mechanisms by which these cells senescences were still unclear. Previous studies have demonstrated that Wnt/β-catenin signaling plays an important role in stem cell senescence. In the current study, we investigated whether Wnt/β-catenin signaling mediates the senescence of BM-MSCs from SLE patients. We have found that Wnt/β-catenin signaling and the p53/p21 pathway were significantly hyperactivated in senescent SLE BM-MSCs. Treatment with 100 ng/mL Dickkopf-1 (DKK1), a Wnt/β-catenin signaling inhibitor or β-catenin siRNA for 48 h could reverse the senescent features of SLE BM-MSCs. Additionally, the expression levels of p53 and p21 were reduced in treated-SLE BM-MSCs compared with the untreated group. In summary, our study indicated that Wnt/β-catenin signaling may play a critical role in the senescence of SLE BM-MSCs through the p53/p21 pathway.

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Acknowledgments

This study was supported by grants from the Chinese National Natural Science Foundation (Nos. 81172841 and 81202368), China Postdoctoral Science Foundation (2013M541708); the Natural Science Foundation of Jiangsu Colleges and Universities Grant (09KJB320010); 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).

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Authors and Affiliations

  1. Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China

    Zhifeng Gu, Wei Tan & Yan Meng

  2. Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China

    Guijuan Feng

  3. Department of Nursing, The Second Affiliated Hospital of Nantong University, Nantong, China

    Biyu Shen

  4. Department of Hematology, Affiliated Hospital of Nantong University, Nantong, China

    Hong Liu

  5. Department of Immunology, Medical College, Nantong University, Nantong, China

    Chun Cheng

Authors
  1. Zhifeng Gu
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  2. Wei Tan
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  3. Guijuan Feng
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  4. Yan Meng
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  5. Biyu Shen
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  6. Hong Liu
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  7. Chun Cheng
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Corresponding authors

Correspondence to Zhifeng Gu or Chun Cheng.

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Zhifeng Gu and Wei Tan have contributed equally to this work.

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Gu, Z., Tan, W., Feng, G. et al. Wnt/β-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway. Mol Cell Biochem 387, 27–37 (2014). https://doi.org/10.1007/s11010-013-1866-5

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  • DOI: https://doi.org/10.1007/s11010-013-1866-5

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