scholarly journals Gene Expression Profile Reveals Abnormalities of Multiple Signaling Pathways in Mesenchymal Stem Cell Derived from Patients with Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Yu Tang ◽  
Xiaolei Ma ◽  
Huayong Zhang ◽  
Zhifeng Gu ◽  
Yayi Hou ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Protein Level ◽  
Mapk Signaling ◽  
Signal Pathways ◽  
Downregulated Gene ◽  
Systemic Lupus ◽  
Multiple Signaling ◽  
Normal Controls

We aimed to compare bone-marrow-derived mesenchymal stem cells (BMMSCs) between systemic lupus erythematosus (SLE) and normal controls by means of cDNA microarray, immunohistochemistry, immunofluorescence, and immunoblotting. Our results showed there were a total of 1, 905 genes which were differentially expressed by BMMSCs derived from SLE patients, of which, 652 genes were upregulated and 1, 253 were downregulated. Gene ontology (GO) analysis showed that the majority of these genes were related to cell cycle and protein binding. Pathway analysis exhibited that differentially regulated signal pathways involved actin cytoskeleton, focal adhesion, tight junction, and TGF-βpathway. The high protein level of BMP-5 and low expression of Id-1 indicated that there might be dysregulation in BMP/TGF-βsignaling pathway. The expression of Id-1 in SLE BMMSCs was reversely correlated with serum TNF-αlevels. The protein level of cyclin E decreased in the cell cycling regulation pathway. Moreover, the MAPK signaling pathway was activated in BMMSCs from SLE patients via phosphorylation of ERK1/2 and SAPK/JNK. The actin distribution pattern of BMMSCs from SLE patients was also found disordered. Our results suggested that there were distinguished differences of BMMSCs between SLE patients and normal controls.

PPARγ expression is increased in systemic lupus erythematosus patients and represses CD40/CD40L signaling pathway

Lupus ◽  
2011 ◽  
Vol 20 (6) ◽  
pp. 575-587 ◽  
Author(s):  
DS Oxer ◽  
LC Godoy ◽  
E Borba ◽  
T Lima-Salgado ◽  
LA Passos ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Pparγ Expression

Deficiency of IRE1 and PERK Signal Pathways in Systemic Lupus Erythematosus

2014 ◽  
Vol 348 (6) ◽  
pp. 465-473 ◽  
Author(s):  
Qiyao Cheng ◽  
Xia Wang ◽  
Yujun Shen ◽  
Yuxian Shen ◽  
Beibei Zu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Signal Pathways ◽  
Systemic Lupus

scholarly journals Study on the Differentially Expressed Genes and Signaling Pathways in Systemic Lupus Erythematosus Using Integrated Bioinformatics Method

2020 ◽  
Author(s):  
Jing Liang ◽  
Xin Zhang ◽  
Wenjia Zhao
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Lupus Erythematosus ◽  
Scientific Research ◽  
Differentially Expressed ◽  
Statistical Hypothesis ◽  
Systemic Lupus ◽  
Ppi Networks ◽  
Geo Database

Abstract Background: Systemic lupus erythematosus (SLE) is a chronic immune connective tissue disease, which is common in women of childbearing age and easy to cause multiple organ inflammatory injury. The occurrence of prostate cancer is the result of multiple factors and genes, but we have little understanding of the mechanism involved. In this study, we deeply explored and analyzed the existing gene data in GEO database in order to find the key genes and new therapeutic targets of SLE.Results: The expression profile dataset of GDS4185, GDS4888, GDS4889 and GDS4890 containing 99 specimens, 42 cases of SLE patients and 57 cases of normal volunteers, were downloaded from the Gene Expression Omnibus (GEO) website. The differentially expressed genes (DEGs) in different tissues was analyzed by statistical hypothesis T test. The gene ontology (GO) enrichment analysis was carried out by the DAVID online tool. KEGG pathway annotation of DEGs was carried out by the KOBAS online computing database. The protein–protein interaction (PPI) networks of the DEGs were built from the STRING website and Cytoscape software. A total of 839 DEGs were calculated from the four GEO datasets. The GO and KEGG analysis indicated that the functions of DEGs mostly participated in the Osteoclast differentiation, HTLV-I infection, Measles, FoxO signaling pathway, Herpes simplex infection, Primary immunodeficiency, Jak-STAT signaling pathway. The following 14 closely related genes, HERC5, TP53, CDC20, GNB2, GNB4, PPP2R1A, GNAI2, PMCH, SOCS3, HERC6, STAT1, SOCS1, ISG15, IFIT3, were key nodes from the PPI network. These genes may have synergistic or indirect interactions with each other in the process of biological metabolism inducing the pathogenesis of SLE.Conclusion: Mining geo database has great scientific research value. In the future, scientific research must fully excavate a variety of database analysis methods. In this study, the screened candidate genes provide effective theoretical basis for the diagnosis, treatment, expected evaluation and related laboratory research of SLE, which are worthy of further experimental verification.

scholarly journals An Overview of the Safety, Efficiency, and Signal Pathways of Stem Cell Therapy for Systemic Lupus Erythematosus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Qian Yang ◽  
Yiping Liu ◽  
Guangyong Chen ◽  
Wancong Zhang ◽  
Shijie Tang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cell ◽  
Autoimmune Disease ◽  
Serum Creatinine ◽  
Signaling Pathways ◽  
Lupus Erythematosus ◽  
Inflammatory Factors ◽  
Signal Pathways ◽  
Systemic Lupus ◽  
Serious Adverse Events

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and tissues. Mesenchymal stem cells (MSCs) are considered a good source for autoimmune disease and hematological disease therapy. This review will summarize the efficacy, safety, and mechanisms of MSC therapy for SLE. MSC therapy can reduce anti-dsDNA, antinuclear antigen (ANA), proteinuria, and serum creatinine in SLE patients. In animal models of SLE, MSC therapy also indicates that it could reduce anti-dsDNA, ANA, proteinuria, and serum creatinine and ameliorate renal pathology. There are no serious adverse events, treatment-related mortality, or tumor-related events in SLE patients after stem cell treatment. MSCs can inhibit inflammatory factors, such as MCP-1 and HMGB-1, and inhibit inflammation-related signaling pathways, such as the NF-κB, JAK/STAT, and Akt/GSK3β signaling pathways, to alleviate the lesions in SLE.

Pyruvate Kinase Isoenzyme M2 Impairs Cognition in Systemic Lupus Erythematosus by Promoting Microglial Synaptic Pruning via β-Catenin Signaling Pathway

2020 ◽  
Author(s):  
Li Lu ◽  
Hailin Wang ◽  
Xuan Liu ◽  
Liping Tan ◽  
Xiaoyue Qiao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Signaling Pathway ◽  
Pyruvate Kinase ◽  
Brain Damage ◽  
Lupus Erythematosus ◽  
Lactate Production ◽  
Systemic Lupus ◽  
Neuronal Synapses ◽  
The Brain

Abstract Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is the severest complication of SLE, which often involves pathological damage to the brain and cognitive function. Glucose metabolic changes are observed in SLE patients with cognitive impairments by medical imaging. Pyruvate kinase isoform M2 (PKM2) is a vital catalyzer of glucose catabolic pathways and in neurological diseases. However, PKM2 regarding the progress of NPSLE remains poorly studied. Thus, this study aimed to analyze and compare the central carbon metabolites in the validated neuropsychiatric lupus model and control mice. Methods MRL/Mp-Faslpr (MRL/lpr) female mice were used as NPSLE mouse model, C57BL6 as control. Metabolomics to assess hippocampa glycolysis level. Glucose, lactic acid, IL-6 and IL-1β of hippocampal were detected by ELISA. The expression of PKM2 was detected by qRT-PCR and western blotting, and the localization of PKM2 in microglia and neurons was assessed with IBA-1, NeuN and PKM2 immunohistochemistry. Flow cytometry was used to detect the number and phenotype of microglia. In vitro, after transfected PKM2 overexpression plasmid on BV2, the effect on microglia and β-catenin signaling pathway were detected. Finally, PKM2 inhibitor Shikonin was injected into MRL/lpr mice, behavioral testing were performed to assess cognition, HE and FJB staining were used to evaluate brain damage.Results Glycolysis was elevated in the hippocampal tissues from MRL/lpr lupus mice, accompanied by an increase in glucose consumption and lactate production. Based on these metabolic variations, PKM2 activation was revealed in hippocampal microglia from lupus mice. Furthermore, PKM2 facilitated microglial phagocytic activity and engulfment of neurons via β-catenin signaling. In vivo, an inhibitor of PKM2, Shikonin, was shown to reduce microglial activation, loss of neuronal synapses, and block β-catenin signaling. Accordingly, the cognitive impairment and brain damage of MRL/lpr mice were relieved. Conclusion These results indicated that abnormal glycolytic metabolism in the brain tissue of NPSLE mice was induced by PKM2 overexpression, which increased the activation of microglia and the ability of phagocytizing neuronal synapses, leading to neuronal loss and cognitive dysfunction in lupus. These phenomena indicated that inhibition on PKM2 would be a novel therapeutic target for the treatment of lupus encephalopathy.

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