title: PTEN/Akt-p27(kip1) Signaling Promote the BM-MSCs Senescence and Apoptosis in SLE Patients.
abstract: 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.
authors: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Department of Emergency, The Yangzhou First People's Hospital, Yangzhou, 225001, China.
authors: Wei
authors: W
authors: Tan
authors: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors: Zhifeng
authors: Z
authors: Gu
authors: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors: Biyu
authors: B
authors: Shen
authors: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors: Jinxia
authors: J
authors: Jiang
authors: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors: Yan
authors: Y
authors: Meng
authors: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors: Zhanyun
authors: Z
authors: Da
authors: Department of Immunology, Medical College, Nantong University, Nantong, 226001, China.
authors: Hong
authors: H
authors: Liu
authors: Department of Immunology, Medical College, Nantong University, Nantong, 226001, China.
authors: Tao
authors: T
authors: Tao
authors: Department of Immunology, Medical College, Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, China.
authors: Chun
authors: C
authors: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: APOPTOSIS; BONE MARROW-MESENCHYMAL STEM CELLS; IMMUNOREGULATION; P27kip1; PTEN/AKT SIGNALING; SENESCENCE; SYSTEMIC LUPUS ERYTHEMATOSUS