ABSTRACT
IgA nephropathy (IgAN) is the most common primary glomerular disease. The characteristic pathology involves immune complexes formed by the deposition of IgA1 and underglycosylated IgA1 aggregates in the mesangial area, which may be accompanied by the deposition of IgG and/or IgM and complement components. However, the molecular mechanisms of IgAN remain unclear. In the present study, microarray analysis showed that the expression of microRNA-630 (miR-630) was significantly reduced in palatal tonsils from IgAN patients compared with chronic tonsillitis. Additionally, bioinformatic analysis showed that Toll-like receptor 4 (TLR4) was the predicted target gene of miR-630 and was regulated by miR-630. When miR-630 was overexpressed in palatal tonsil mononuclear cells from IgAN patients, the expression of TLR4 was reduced and the content of IgA1 in the cell culture supernatant was decreased, and the level of galactosylation in the IgA1 hinge region was increased. Moreover, immunohistochemical analysis showed that the expression of TLR4 in IgAN patients was significantly increased. After knocking down the expression of TLR4, both the concentration of IgA1 and the binding force of IgA1 with broad bean lectin were significantly reduced in IgAN. Furthermore, the mechanism study demonstrated that TLR4 might regulate the expression of IL-1ß and IL-8 through NF-κB signaling pathway to modulate the concentration of IgA1 and the glycosylation level of IgA1. This interesting finding may offer new insight into the molecular mechanism of IgAN.
Subject(s)
Glomerulonephritis, IGA/immunology , Immunoglobulin A/biosynthesis , MicroRNAs/metabolism , Palatine Tonsil/immunology , Toll-Like Receptor 4/metabolism , Adolescent , Adult , Biomarkers/metabolism , Cells, Cultured , Child , Female , Gene Knockdown Techniques , Glycosylation , Humans , Interleukin-1beta/metabolism , Interleukin-8/metabolism , Male , MicroRNAs/genetics , NF-kappa B/metabolism , Palatine Tonsil/pathology , Signal Transduction/genetics , Transfection , Young AdultABSTRACT
Objective To investigate the clinicopathological relation between the TNF-? and IgA nephropathy. Methods TNF-? levels in serum, urine and renal tissues of 50 patients with IgA nephropathy were measured, and 10 patients with minimal change nephrotic syndrome(MCNS) and 10 healthy subjects served as negative control group. Results The serum and urine levels of TNF-? in the patients with IgA nephropathy were significantly higher than those in the patients with MCNS and healthy subjects, and had a significant positive correlation with the degree of proteinuria and renal demage. TNF-? expression was mainly localized in the cytoplasm of the proximal renal tubular epithelial cells, and the interstitium with more monocyte-macrophages infiltration. Conclusion TNF-? took part in the onset of hematuria and proteinuria, was correlated with the degree of renal damage, and played an important role in the aggravation of IgA nephropathy.
