title: Wnt/β-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway.
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.
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China, guzhifeng@126.com.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Guijuan
authors.initials: G
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Biyu
authors.initials: B
authors.lastname: Shen
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000502:physiology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; C495270:CTNNB1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin