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DNA induction of MDM2 promotes proliferation of human renal mesangial cells and alters peripheral B cells subsets in pediatric systemic lupus erythematosus
- Source :
- Molecular immunology. 94
- Publication Year :
- 2017
-
Abstract
- The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC). We also proved that elevated apoptotic and necrotic CD4+T cells were the main cause for increased plasma levels of cfDNA in pSLE. Additionally, upon DNA transfection MDM2 increased while P53 and P21 decreased in human renal mesangial cells (HRMC), with concomitant increase in proliferation rate and proportion of cells in S phase, as demonstrated by cell proliferation assay and cell cycle analysis. However, MDM2 inhibition reversed the trend. Furthermore, percentage of switched memory B cells decreased and proportion of double negative B cells increased upon blockage of MDM2 in PBMC. In summary, our study provided the first evidence that DNA induction of MDM2 promotes proliferation of HRMC and alters peripheral B cells subsets in pSLE. Thus our study has not only elucidated the pathogenesis of MDM2 in pediatric LN but also provided a novel target for drug development. In conclusion, our data suggested that apoptosis, cfDNA and MDM2 could form a pathological axis in SLE, especially in pSLE.
- Subjects :
- 0301 basic medicine
Immunology
Lupus nephritis
B-Lymphocyte Subsets
Plasma cell
Peripheral blood mononuclear cell
Flow cytometry
Pathogenesis
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Lupus Erythematosus, Systemic
Lymphocyte Count
Child
Molecular Biology
Cells, Cultured
Cell Proliferation
B-Lymphocytes
medicine.diagnostic_test
Chemistry
Cell growth
Gene Expression Regulation, Developmental
Cell Differentiation
Proto-Oncogene Proteins c-mdm2
medicine.disease
Molecular biology
030104 developmental biology
medicine.anatomical_structure
Apoptosis
030220 oncology & carcinogenesis
Case-Control Studies
Mesangial Cells
CD8
Subjects
Details
- ISSN :
- 18729142
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Molecular immunology
- Accession number :
- edsair.doi.dedup.....073bdfe5afa5884035878d1aa1a6a41d