The effects of leptin on the senescence of bone marrow-derived mesenchymal stem cells, frequencies of immune cells and lupus disease in MRL/Ipr mice
10.3760/cma.j.issn.1007-7480.2018.08.003
- VernacularTitle:瘦素对骨髓间充质干细胞及免疫细胞亚群的调控作用及其对狼疮鼠病情的影响
- Author:
Haifeng CHEN
1
;
Yaohong ZOU
;
Lingyun SUN
Author Information
1. 214023,南京医科大学附属无锡人民医院风湿免疫科
- Keywords:
Leptin;
Lupus erythematosus,systemic;
Cell senescence;
Mesenchymal stem cell;
Immune regulation
- From:
Chinese Journal of Rheumatology
2018;22(8):516-521
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of leptin on the senescence of bone marrow-derived mesenchymal stem cells,frequencies of Treg and Th17 cells,and lupus disease in MRL/lpr mice,and to explore the pathogenesis of systemic lupus erythematosus (SLE).Methods Leptin (1 μg/g) or phosphate buffer saline (PBS) was injected into C57BL/6 (B6) mice,ob/ob mice and MRL/lpr mice intra-peritoneally.Urine protein was examined by Coomassie brilliant blue method.The levels of serum leptin,antinuclear antibody (ANA),anti-dsDNA antibody and immunoglobulin (Ig)G were detected by enzyme linked immunosorbent assay (ELISA).Bone marrow derived mesenchymal stem cells (MSCs) were isolated,and treated with or without leptin,then the senescence of MSCs were evaluated by SA-β-gal staining,the levels of p53 and p21 mRNA were measured by real time polymerase chain reaction (PCR),the protein levels of p53 and p21 were tested by Westem blotting method.Data were analyzed with t test and ANOVA.Results The level of serum leptin was higher in MRL/lpr mice than that of B6 mice [(4.5±0.8) ng/ml vs (2.3±0.5) ng/ml,t=2.38,P＜0.05].Leptin treatment in vivo accelerated the senescence of bone marrow-derived MSCs from all B6 mice,lupus mice and ob/ob mice,manifestedas increased frequencies of SA-β-gal positive cells [(20.6±0.6)％ vs (15.4±1.6)％,t=8.09,P＜0.05],higher levels of mRNA and p53 and p21 protein.Leptin treatment in vivo also down-regulated the frequency of Treg cells [(2.77±0.23)％ vs (5.01±0.18)％ t=3.91,P＜0.01],and up-regulated Th17 cells [(2.24± 0.11)％ vs (1.74±0.07)％,t=5.013,P＜0.01].The titer of ANA was further increased in leptin-treated MRL/lpr mice [(288±69) U/ml vs (190±90) U/ml,t=2.84,P＜0.05].The levels of serum anti-dsDNA antibody were also remarkably elevated [(12 399±1 237) U/ml vs (6 217±1 304) U/ml,t=3.44,P＜0.01].Leptin could increase the secretion of total IgG [MRL/Ipr (27.2±2.9) mg/ml vs (25.0±3.3) mg/ml,t=3.07,P＜0.05].The proteinuria concentration was increased in lupus mice [(1.00±0.10) mg/ml vs (0.81 ±0.06) mg/ml,t=3.31,P＜0.05],demonstrating that leptin accelerates lupus nephritis.Conclusion Leptin administr-ation in vivo enhances the senescence of bone marrow derived MSCs,dys-regulate of Treg/Th17 cells from MRL/Ipr mice,which impaires the role of immuno-modulation,and aggravates the progress of lupus disease.
