ABSTRACT
BACKGROUND: Increasing evidence has indicated that circular RNAs (circRNAs) play a role in various diseases. However, the influence of circRNAs in nephritis remains unknown. METHODS: Microarray analysis and RT-qPCR were used to detect the expression of circRNA. Type I IFN were administrated to RMC and HEK293 cells to establish a nephritis cell model. CCK-8, MTT assay, and flow cytometry were used to assess cell proliferation, viability, and apoptosis of cells. Bioinformatics analysis and dual luciferase reporter assay detect the interaction of circ_0007059, miRNA-1278, and SHP-1. Glomerulonephritis was performed in a mouse model by administration of IFNα-expressing adenovirus. IHC staining showed the pathogenic changes. RESULTS: In the present study, the expression of circ_0007059 in type I interferon (IFN)-treated renal mesangial cells (RMCs), lupus nephritis (LN) specimens, and HEK293 cells was downregulated compared with that in normal healthy samples and untreated cells. Circ_0007059 overexpression resulted in increased cell proliferation, cell viability, apoptosis, and inflammation-associated factors (CXCL10, IFIT1, ISG15, and MX1) in RMCs and HEK293 cells. In addition, circ_0007059 overexpression significantly restored cell proliferation and viability and inhibited IFN-induced apoptosis. Further, the increased expression resulted in reduced inflammation and the downregulation of CXCL10, IFIT1, ISG15, and MX1 in RMCs and HEK293 cells. Circ_0007059 serves as a sponge for miR-1278 so that the latter can target the 3'-untranslated region of SHP-1. Overexpressed circ_0007059 inhibited miR-1278 expression and elevated SHP-1 expression, subsequently reducing STAT3 phosphorylation. Meanwhile, miR-1278 was upregulated and SHP-1 was downregulated in LN samples and IFN-treated cells. The restoration of miR-1278 counteracted the effect of circ_0007059 on viability, apoptosis, and inflammation as well as on SHP-1/STAT3 signaling in RMCs and HEK293 cells. We also investigated the role of SHP-1 overexpression in IFN-treated RMCs and HEK293 cells; SHP-1 overexpression resulted in a similar phenotype as that observed with circ_0007059 expression. CONCLUSIONS: The study indicates that circ_0007059 protects RMCs against apoptosis and inflammation during nephritis by attenuating miR-1278/SHP-1/STAT3 signaling.
Subject(s)
Gene Expression Regulation , MicroRNAs/genetics , Nephritis/etiology , Nephritis/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics , RNA, Circular , STAT3 Transcription Factor/metabolism , Signal Transduction , Adult , Animals , Biomarkers , Cell Line , Disease Models, Animal , Disease Susceptibility , Female , Flow Cytometry , Humans , Immunohistochemistry , Lupus Nephritis , Male , Mice , Middle Aged , Nephritis/pathology , Young AdultABSTRACT
OBJECTIVE: To investigate the relationship between T cell receptor constant alpha chain (TCRCα) gene +1592C/T polymorphism and IgA nephropathy. METHODS: TCRCα +1592C/T genotypes were identified by PCR-RFLP and direct sequencing in 244 Chinese Han patients with IgA nephropathy, who were classified according to their genotype into CC (188 cases), CT (54 cases) and TT (2 cases) groups. The clinical and pathological data of the patients were analyzed in relation to the TCRCα +1592C/T genotypes. RESULTS: No significant differences in the clinical and biochemical indices were found in these patients with different TCRCα gene +1592C/T genotypes. TCRCα +1592C/T polymorphism was not found to contribute to severity or manifestations of renal pathology. CONCLUSIONS: TCRCα+1592C/T polymorphism may not be associated with the susceptibility to IgA nephropathy in the Chinese Han population.
