Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. METHODS: Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. RESULTS: 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-ß1 (TGF-ß1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). CONCLUSION: Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

Behcet's disease with peripheral nervous system involvement successfully treated with golimumab: a case report and review of the literature.

Nervous system involvement is a rare and serious complication of Behcet's disease (BD), and the peripheral type is rarer. This article aimed to describe a case of BD with the peripheral nervous system (PNS) involvement and present a comprehensive literature review. One case of BD with PNS involvement was reported and related literature was retrospectively reviewed via PubMed/MEDLINE and Scopus database. The patient was resistant to traditional treatments, such as glucocorticoids and immunosuppressants, but had rapid quiescence after using golimumab. Our literature review suggests that the involved peripheral nerves in BD were diverse, the most common were the tibial nerves and peroneal nerves, vasculitis might be the main cause, and prednisone was still the cornerstone of treatment. TNF-α inhibitors have been increasingly used for refractory BD in recent years. This well-illustrated case demonstrates the potential benefit of golimumab to the patient with PNS involvement. Given the diversity and complexity of PNS involvement, we recommend golimumab as a new trial treatment in clinical practice.

Identification of Molecular Markers Associated With the Pathophysiology and Treatment of Lupus Nephritis Based on Integrated Transcriptome Analysis.

Lupus nephritis (LN) is a well-known complication of systemic lupus erythematosus and is its leading cause of morbidity and mortality. Our study aimed to identify the molecular markers associated with the pathophysiology and treatment of LN. The renal tissue gene expression profiles of LN patients in the GSE32591 dataset were downloaded as a discovery cohort from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified; weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules of DEGs; and gene function enrichment analysis, molecular crosstalk analysis, and immune cell infiltration analysis were performed to explore the pathophysiological changes in glomeruli and tubulointerstitia of LN patients. The crosstalk genes were validated in another RNA-sequencing cohort. DEGs common in RNA-sequencing dataset and GSE32591 were uploaded to the Connectivity Map (CMap) database to find prospective LN-related drugs. Molecular docking was used to verify the targeting association between candidate small molecular compounds and the potential target. In all, 420 DEGs were identified; five modules and two modules associated with LN were extracted in glomeruli and tubulointerstitia, respectively. Functional enrichment analysis showed that type I interferon (IFN) response was highly active, and some biological processes such as metabolism, detoxification, and ion transport were impaired in LN. Gene transcription in glomeruli and tubulointerstitia might affect each other, and some crosstalk genes, such as IRF7, HLA-DRA, ISG15, PSMB8, and IFITM3, play important roles in this process. Immune cell infiltration analysis revealed that monocytes and macrophages were increased in glomeruli and tubulointerstitia, respectively. CMap analysis identified proscillaridin as a possible drug to treat LN. Molecular docking showed proscillaridin forms four hydrogen bonds with the SH2 domain of signal transducer and activator of transcription 1 (STAT1). The findings of our study may shed light on the pathophysiology of LN and provide potential therapeutic targets for LN.

Vitamin D protects podocytes from autoantibodies induced injury in lupus nephritis by reducing aberrant autophagy.

SUBJECT: The aim of this study was to investigate whether vitamin D plays a protective role in podocyte injury induced by autoantibodies purified from the serum of patients with lupus nephritis (LN) via reducing aberrant autophagy. METHODS: Autophagic activities of renal tissues of patients with LN were evaluated under transmission electronic microscope (TEM). Immunoglobulin G (IgG) from patients with LN was purified to induce human podocyte injury, and the role of vitamin D in injury was observed. Podocytes were observed under TEM, autophagic activity was evaluated by western blot analysis and quantitative real-time polymerase chain reaction, and mRFP-GFP-LC3B adenovirus was infected into human podocytes in vitro. RESULTS: Significantly higher autophagic levels were observed in patients with LN (P <0.05), and apparently greater autophagic levels in podocytes were shown (P <0.05). Among different classifications of LN, class V (n = 5), III + V (n = 5), and IV + V (n = 5) gained higher autophagic levels than class III (n = 5) and IV (n = 5). Induced autophagy, which was evident by increased LC3B-II and Beclin 1 level, caused consumption of p62, more autophagosomes observed under TEM, and more LC3B dots observed under confocal microscope in the IgG group, along with decreased nephrin expression, which suggests podocyte injury. Reduction of autophagy as well as alleviated podocyte injury was observed in the IgG+ vitamin D group. CONCLUSION: This study demonstrates that vitamin D plays a protective role in podocyte injury induced by autoantibodies from patients with LN and appears to be a novel therapy target in LN.

Induction therapy downregulates the expression of Th17/Tfh cytokines in patients with active lupus nephritis.

To determine the potential changes of IL-6, IL-17A and IL-21 levels during induction therapy, and to assess their relationship with disease activity and immunologic features on patients with active lupus nephritis, twenty-eight patients treated with corticosteroid and immunosuppressants were included in this study. Demographic, clinical, serological data and disease activity were assessed. Blood samples were collected at week 0, 12 and 24, and serum concentrations of IL-17A, IL-6 and IL-21 were measured by cytometric bead array. The serum concentrations of IL-6, IL-17A and IL-21 (P<0.001, P<0.01, P=0.001, respectively) decreased progressively during induction therapy. Concentration of IL-6, IL-17A and IL-21 was higher in non-remission group than that in remission group. A positive correlation was established between the concentration of these cytokines and the severity of proteinuria (P<0.001, P=0.020, P=0.045, respectively), ESR (P<0.001), SLEDAI scores (P<0.05), and ANA titers (P=0.018, P=0.048, P<0.05, respectively). Additionally, ROC curve analysis for IL-6, IL-17A and IL-21 was performed to predict the disease activity. The optimal cutoff level was 5.78 pg/ml, 1.98 pg/ml and 8.59 pg/ml, with AUC=0.809, 0.735 and 0.786. The concentration of IL-6 and IL-21 may be regarded as an indicator for the remission of active lupus nephritis, with cutoff value of 9.12 pg/ml and 11.30 pg/ml, while AUC=0.930 and 0.896. The production of serum IL-6, IL-17A and IL-21 in active LN was dramatically declined during induction therapy, which may improve disease activity while delay disease progression of LN.