Dataset Information

MicroRNA-630 Regulates Underglycosylated IgA1 Production in the Tonsils by Targeting TLR4 in IgA Nephropathy.

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-1? and IL-8 through NF-?B 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.

SUBMITTER: Liu C

PROVIDER: S-EPMC7725902 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

microRNA-630 Regulates Underglycosylated IgA1 Production in the Tonsils by Targeting TLR4 in IgA Nephropathy.

Liu Chan C Ye Mu-Yao MY Yan Wen-Zhe WZ Peng Xiao-Fei XF He Li-Yu LY Peng You-Ming YM

Frontiers in immunology 20201126

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 ton ...[more]

PMID: 33324395

Similar Datasets

Project description:BackgroundImmunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.MethodsThirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.ResultsIn patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932-1; P < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels (P < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. Actinobacteria, Bifidobacterium, Blautia, Bifidobacteriaceae, and Bifidobacteriales were decreased and Shigella was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.ConclusionThe urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.

Dataset Information

MicroRNA-630 Regulates Underglycosylated IgA1 Production in the Tonsils by Targeting TLR4 in IgA Nephropathy.

Publications

microRNA-630 Regulates Underglycosylated IgA1 Production in the Tonsils by Targeting TLR4 in IgA Nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets