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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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.
KeywordsBone marrow-mesenchymal stem cells (BM-MSCs) Systemic lupus erythematosus (SLE) Senescence Wnt/β-Catenin signaling p53/p21 pathway
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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