Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA134229 | ENA |
REPOSITORIES: ENA
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Project description:Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide characterized by aberrant O-glycosylation in the hinge region of IgA1. The basis for the abnormal glycosylation in IgAN is still unknown, but an important involvement of the enzyme core 1, beta 1,3-galactosyltransferase 1 (C1GALT1) is known. However, the role of microRNAs (miRNAs), a new family of key mRNA regulatory molecules, in the IgAN pathogenesis has not yet been reported. In this study, by high-throughput microRNA profiling, we identified 37 miRNAs differentially expressed in peripheral blood mononuclear cells (PBMCs) from IgAN patients compared to healthy subjects. Among them, upregulated miR-148b potentially targeted C1GALT1, INVS and PTEN, three genes notably downregulated in IgAN patients. C1GALT1 expression levels in IgAN patients were reduced and negatively correlated with the upregulated miR-148b expression. We demonstrated the biological relationship between miR-148b and C1GALT1 by transient transfection experiments ex vivo. When we reduced the upregulated miR-148b function in PBMCs of IgAN patients an increase of the C1GALT1 mRNA and protein levels was observed. We validated biologically also the miR-148b targeting of INVS , involved in the altered modulation of the WNT–β-catenin and PI3K/Akt pathways in IgAN patients. All together our data evidence an important role of miR-148b in the pathogenesis of IgAN, which could explain the aberrant glycosylation of IgA1 in the pathogenesis and should light on a potential target for the theraphy of the disease.
2012-03-12 | GSE25590 | GEO
Project description:Purpose: Increases in galactose-deficient IgA1 (Gd-IgA1) play a crucial role in the pathogenesis of IgA nephropathy (IgAN), and several recent experiments have shown that microRNAs (miRNAs) are involved in regulating the development and physiological function of the kidney. The aims of this study were to identify miRNAs that can affect the pathogenesis of IgAN and reveal the underlying regulatory mechanism of IgA1 glycosylation in peripheral blood Methods: The differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) between IgAN patients and healthy controls were screened by high-throughput sequencing. The miRNA targets were predicted and verified by dual-luciferase reporter assays. We also explored the miRNA regulation of Gd-IgA1 through the transfection of miRNA mimics and related plasmids Results: The high-throughput sequencing results showed that miR-98-5p was highly expressed in the PBMCs of IgAN patients compared with healthy controls, and the luciferase reporter gene system confirmed that miR-98-5p might target chemokine ligand 3 (CCL3). The transfection of si-CCL3 confirmed that a decrease in CCL3 can affect the expression of interleukin-6 (IL-6) and C1GALT1. The overexpression of miR-98-5p in PBMCs via the transfection of miR-98-5p mimic reduced the CCL3 and C1GALT1 levels and increased the IL-6 levels. However, these changes in PBMCs were attenuated by cotransfection with the CCL3 plasmid. Conclusion: The results showed that miR-98-5p in PBMCs can target CCL3 to decrease its expression, which increased the IL-6 levels and the resulting increase in IL-6 can decrease C1GALT1 expression. Therefore, miR-98-5p might be involved in the development of IgAN.
2023-02-20 | GSE145652 | GEO
Project description:miR-148b modulates the expression of multiple genes
| PRJNA142189 | ENA
Project description:The upregulation of miR-98-5p affects the glycosylation of IgA1 through cytokines in IgA nephropathy
| PRJNA607802 | ENA
Project description:Previous studies revealed the abnormal lymphocytes subsets in IgA nephropathy (IgAN). Recently, emerging studies indicate that microRNA could influence the balance of T helper differentiation and function. Here we explore the underlying mechanism regarding how miRNA regulated lymphocytes subsets in IgAN, focused on T helper cell polarization.
2021-01-01 | GSE125998 | GEO
Project description:Previous studies revealed the abnormal lymphocytes subsets in IgA nephropathy (IgAN). Recently, emerging studies indicate that microRNA could influence the balance of T helper differentiation and function. Here we explore the underlying mechanism regarding how miRNA regulated lymphocytes subsets in IgAN, focused on T helper cell polarization.
2021-01-01 | GSE125818 | GEO
Project description:To identify which miR-148b targets were involved in tumorigenesis, a microarray analysis was performed for miR-148b over-expressing cells versus controls and 129 (49 up and 80 down) modulated genes were revealed. The effects of miR-148b on cancer progression depend on the direct and indirect regulation of multiple target genes. To identify miR-148b modulated genes, MDA-MB-231 cells were transfected with miR-148b precursors or negative controls (pre-miR-148b or control) and used 48h later for microarray and western blot (WB) analyses. When a âWhole Human Genome Oligo Microarrayâ (Agilent) platform was employed, 129 differentially expressed genes (49 upregulated, 80 downmodulated) were found at 48h, considering a fold change (FC) cut of 1.5 and a false discovery rate (FDR) of 16% (Table S4). Crossing these results with the list of putative miR-148b targets (3642) obtained by the miRecords System, we observed that 33 of the modulated genes were also miR-148b predicted targets and interestingly, 26 out of these 33 genes were downmodulated.
2012-12-16 | E-GEOD-26662 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE35487: Expression data from human with IgA nephropathy (IgAN) [HG-U133A] GSE35488: Expression data from human with IgA nephropathy (IgAN) [HG-U133A_ENTREZG_10] Refer to individual Series
2012-02-02 | E-GEOD-35489 | biostudies-arrayexpress
Project description:IgA nephropathy represents the most prevalent chronic nephrosis worldwide. However, pathogenesis about IgA deposition and end-stage renal failure is still not well defined. Using single-cell RNA-seq, we identified the mesangial membrane receptor for IgA, which collaborates with increased extracellular matrix proteins and protease inhibitor to facilitate IgA deposition. Meanwhile, cell-cell interaction analysis revealed increased communications between mesangium and other cell types, uncovering how morbidity inside glomerulus spreads to whole kidney, which results in the genetic changes of kidney resident immune cells. Prominent interaction decreasing in intercalated cells leads to the discovery of a transitional cell type, which exhibited significant EMT and fibrosis features. Our work comprehensively characterized the pathological mesangial signatures, highlighting the step-by-step pathogenic process of IgA nephropathy from mesangium to epithelium.
2021-07-06 | GSE127136 | GEO
Project description:The current study makes use of NanoString targeted technology to profile urinary exosomal miRNAs from IgA nephropathy affected patients and corresponding healthy controls. Circulatory biomarkers were detected for IgA nephropathy from Indian cohort which can be made used for the diagnostic therapy. 14 miRNAs were detected to be related to the disregulation in miRNome of IgA nephropathy patients using lasso feature selection method, out of which multiple miRNAs like hsa.mir.146b.3p, hsa.mir.599 and many more was resulted with high AUROC values >=0.9 efficient in differentiating between healthy controls and IgA nephropathy condition. These markers can be use further in the diagnosis and treatment of IgAN.
2023-12-13 | GSE244625 | GEO