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PTEN/Akt‐p27 kip1 Signaling Promote the BM‐MSCs Senescence and Apoptosis in SLE Patients
Author(s) -
Tan Wei,
Gu Zhifeng,
Shen Biyu,
Jiang Jinxia,
Meng Yan,
Da Zhanyun,
Liu Hong,
Tao Tao,
Cheng Chun
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25112
Subject(s) - tensin , pten , protein kinase b , mesenchymal stem cell , cancer research , senescence , annexin , pi3k/akt/mtor pathway , proinflammatory cytokine , chemistry , biology , signal transduction , immunology , medicine , microbiology and biotechnology , inflammation , flow cytometry
Recent studies showed that allogeneic bone marrow (BM)‐mesenchymal stem cells transplantation (MSCT) was effective in systemic lupus erythematosus (SLE) patients and lupus‐prone mice. However, syngeneic BM‐MSCT was ineffective. Previous studies, including ours, revealed that BM‐MSCs from SLE patients exhibited early signs of senescence and apoptosis such as slow proliferation, increasing senescence‐associated β‐galactosidase (SA‐β‐gal)‐positive cells and Annexin V‐positive cells, and caspase cascade activation. The abnormalities of BM‐MSCs might be associated with the pathogenesis of SLE. In this study, we aimed to determine the molecular mechanism of senescent BM‐MSCs from SLE patients. We found that the expression of protein 27 kinase inhibition protein 1(p27 kip1 ) increased significantly, which was regulated by phosphatase and tensin homology deleted on chromosome 10 (PTEN)/protein kinase B (Akt) signaling in SLE BM‐MSCs. Knockdown of PTEN or p27 kip1 could reverse the senescent features of BM‐MSCs via down‐regulating p27 kip1 expression. When purified CD4 + T cells were incubated with PTEN or p27 kip1 ‐silenced SLE BM‐MSCs, the ratio of regulatory T (Treg)/T helper type 17 (Th17) cells increased significantly by enhancing regulatory cytokines (IL‐10 and TGF‐β) and reducing pro‐inflammatory cytokines (IL‐17 and IL‐6). Taken together, we demonstrated that PTEN/Akt signaling played an essential role in the senescent and apoptotic BM‐MSCs from SLE patients by up‐regulating p27 kip1 expression. J. Cell. Biochem. 116: 1583–1594, 2015. © 2015 Wiley Periodicals, Inc.