scholarly journals The molecular mechanisms of inflammation and scarring in the kidneys of immunoglobulin A nephropathy

2021 ◽  
Author(s):  
Francesco Paolo Schena ◽  
Michele Rossini ◽  
Daniela Isabel Abbrescia ◽  
Gianluigi Zaza
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Renal Tissue ◽  
Urinary Biomarkers ◽  
Specific Gene ◽  
Rna Seq ◽  
Immunoglobulin A Nephropathy ◽  
Renal Lesions

AbstractKidney biopsy is the cornerstone for the diagnosis of immunoglobulin A nephropathy (IgAN). The immunofluorescence technique evidences the IgA deposits in the glomeruli; the routine histology shows degree of active and chronic renal lesions. The spectrum of renal lesions is highly variable, ranging from minor or no detectable lesions to diffuse proliferative or crescentic lesions. Over the past three decades, renal transcriptomic studies have been performed on fresh or frozen renal tissue, and formalin-fixed paraffin-embedded kidney tissue specimens obtained from archival histological repositories. This paper aims to describe (1) the transcriptomic profiles of the kidney biopsy and (2) the potential urinary biomarkers that can be used to monitor the follow-up of IgAN patients. The use of quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), microarrays and RNA-sequencing (RNA-seq) techniques on renal tissue and separated compartments of the nephron such as glomeruli and tubule-interstitium has clarified many aspects of the renal damage in IgAN. Recently, the introduction of the single-cell RNA-seq techniques has overcome the limitations of the previous methods, making that it is possible to study the whole renal tissue without the dissection of the nephron segments; it also allows better analysis of the cell-specific gene expression involved in cell differentiation. These gene products could represent effective candidates for urinary biomarkers for clinical decision making. Finally, some of these molecules may be the targets of old drugs, such as corticosteroids, renin–angiotensin–aldosterone blockers, and new drugs such as monoclonal antibodies. In the era of personalized medicine and precision therapy, high-throughput technologies may better characterize different renal patterns of IgAN and deliver targeted treatments to individual patients.

Expression of response gene to complement-32 in renal tissue of children with immunoglobulin A nephropathy

2011 ◽  
Vol 45 (5) ◽  
pp. 371-376 ◽  
Author(s):  
Xiao-Ling Niu ◽  
Xin-Yu Kuang ◽  
Zhi-Gang Zhang ◽  
Xue-Guang Liu ◽  
Zhong-Hua Zhao ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Renal Tissue ◽  
Immunoglobulin A Nephropathy ◽  
Response Gene

Plasma fractalkine levels are associated with renal inflammation and outcomes in immunoglobulin A nephropathy

2018 ◽  
Vol 34 (9) ◽  
pp. 1549-1558 ◽  
Author(s):  
Ran Luo ◽  
Shui-Ming Guo ◽  
Yue-Qiang Li ◽  
Yi Yang ◽  
Meng-Lan Li ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Creatinine Level ◽  
Mesangial Cells ◽  
Immunoglobulin A ◽  
Renal Tissue ◽  
Chinese Patients ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Urine Protein ◽  
Mesangial Hypercellularity

Abstract Background A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients. Methods Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed. Results The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7. Conclusions Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN.

scholarly journals Chromatin-enriched RNAs mark active and repressive cis-regulation: an analysis of nuclear RNA-seq

2019 ◽  
Author(s):  
Xiangying Sun ◽  
Zhezhen Wang ◽  
Carlos Perez-Cervantes ◽  
Alex Ruthenburg ◽  
Ivan Moskowitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Specific Gene ◽  
Rna Seq ◽  
Cell Type ◽  
Neighboring Gene ◽  
Cis Regulation ◽  
Nuclear Rna ◽  
Cell Type Specific

AbstractLong noncoding RNAs (lncRNAs) localize in the cell nucleus and influence gene expression through a variety of molecular mechanisms. RNA sequencing of two biochemical fractions of nuclei reveals a unique class of lncRNAs, termed chromatin-enriched nuclear RNAs (cheRNAs) that are tightly bound to chromatin and putatively function to cis-activate gene expression. Until now, a rigorous analytic pipeline for nuclear RNA-seq has been lacking. In this study, we survey four computational strategies for nuclear RNA-seq data analysis and show that a new pipeline, Tuxedo, outperforms other approaches. Tuxedo not only assembles a more complete transcriptome, but also identifies cheRNA with higher accuracy. We have used Tuxedo to analyze gold-standard K562 cell datasets and further characterize the genomic features of intergenic cheRNA (icheRNA) and their similarity to those of enhancer RNA (eRNA). Moreover, we quantify the transcriptional correlation of icheRNA and adjacent genes, and suggest that icheRNA may be the cis-acting transcriptional regulator that is more positively associated with neighboring gene expression than eRNA predicted by state-of-art method or CAGE signal. We also explore two novel genomic associations, suggesting cheRNA may have diverse functions. A possible new role of H3K9me3 modification coincident with icheRNA may be associated with active enhancer derived from ancient mobile elements, while a potential cis-repressive function of antisense cheRNA (as-cheRNA) is likely to be involved in transiently modulating cell type-specific cis-regulation.Author SummaryChromatin-enriched nuclear RNA (cheRNA) is a class of gene regulatory non-coding RNAs. CheRNA provides a powerful way to profile the nuclear transcriptional landscape, especially to profile the noncoding transcriptome. The computational framework presented here provides a reliable approach to identifying cheRNA, and for studying cell-type specific gene regulation. We found that intergenic cheRNA, including intergenic cheRNA with high levels of H3K9me3 (a mark associated with closed/repressed chromatin), may act as a transcriptional activator. In contrast, antisense cheRNA, which originates from the complementary strand of the protein-coding gene, may interact with diverse chromatin modulators to repress local transcription. With our new pipeline, one future challenge will be refining the functional mechanisms of these noncoding RNA classes through exploring their regulatory roles, which are involved in diverse molecular and cellular processes in human and other organisms.

A Comparative Study of the Gut Microbiota Associated with Immunoglobulin A Nephropathy and Membranous Nephropathy

2020 ◽  
Author(s):  
shiren sun ◽  
Ruijuan Dong ◽  
Ming Bai ◽  
Jin Zhao ◽  
Di Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Membranous Nephropathy ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Amplicon Sequencing ◽  
Healthy Controls ◽  
Immunoglobulin A Nephropathy ◽  
Positive Correlation ◽  
16S Rdna Amplicon Sequencing ◽  
The Oxford Classification

Abstract Background The pathogenesis of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) is characterized by immune dysregulation, which is related to gut dysbiosis. The aim of the study was to compare the gut microbiota of patients with IgAN and MN versus healthy controls. We used 16S rDNA amplicon sequencing to investigate the bacterial communities of 44 patients with kidney biopsy-proven IgAN, 40 patients with kidney biopsy-proven MN, and 30 matched healthy controls (HC). Results The abundance of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis were significantly higher in IgAN than in HC, whereas lower abundances were observed for Roseburia, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Fusobacterium . Furthermore, the abundance of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis , Streptococcus, and Enterobacteriaceae_ unclassified increased, while that of Lachnospira, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Veillonella decreased in MN. The abundance of Megasphaera and Bilophila was higher, whereas that of Megamonas, Veillonella, Klebsiella, and Streptococcus was lower in patients with IgAN than in those with MN. Analysis of the correlations showed that in the IgAN group, Prevotella was positively correlated, while Klebsiella , Citrobacter, and Fusobacterium were negatively correlated with the level of serum albumin. Positive correlation also existed between Bilophila and Crescents in the Oxford classification of IgAN. In the MN group, negative correlation was observed between Escherichia-Shigella and proteinuria, Bacteroides and Klebsiella showed positive correlation with the MN stage. Conclusions Patients with IgAN and MN exhibited gut microbial signatures distinct from healthy controls. Our study suggests the potential of gut microbiota as specific biomarker and contributor in the pathogenesis of IgAN and MN.

scholarly journals Formalin-fixed paraffin-embedded renal biopsy tissues: an underexploited biospecimen resource for gene expression profiling in IgA nephropathy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sharon Natasha Cox ◽  
Samantha Chiurlia ◽  
Chiara Divella ◽  
Michele Rossini ◽  
Grazia Serino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Iga Nephropathy ◽  
Clinical Decision Making ◽  
Expression Profiles ◽  
Specific Gene ◽  
Renal Lesions ◽  
Formalin Fixed Paraffin ◽  
Renal Biopsies ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract Primary IgA nephropathy (IgAN) diagnosis is based on IgA-dominant glomerular deposits and histological scoring is done on formalin-fixed paraffin embedded tissue (FFPE) sections using the Oxford classification. Our aim was to use this underexploited resource to extract RNA and identify genes that characterize active (endocapillary–extracapillary proliferations) and chronic (tubulo-interstitial) renal lesions in total renal cortex. RNA was extracted from archival FFPE renal biopsies of 52 IgAN patients, 22 non-IgAN and normal renal tissue of 7 kidney living donors (KLD) as controls. Genome-wide gene expression profiles were obtained and biomarker identification was carried out comparing gene expression signatures a subset of IgAN patients with active (N = 8), and chronic (N = 12) renal lesions versus non-IgAN and KLD. Bioinformatic analysis identified transcripts for active (DEFA4,TNFAIP6,FAR2) and chronic (LTB,CXCL6, ITGAX) renal lesions that were validated by RT-PCR and IHC. Finally, two of them (TNFAIP6 for active and CXCL6 for chronic) were confirmed in the urine of an independent cohort of IgAN patients compared with non-IgAN patients and controls. We have integrated transcriptomics with histomorphological scores, identified specific gene expression changes using the invaluable repository of archival renal biopsies and discovered two urinary biomarkers that may be used for specific clinical decision making.

Kidney biopsy in glomerular disease: a hospital based study

2017 ◽  
Vol 4 (1) ◽  
pp. 38-41
Author(s):  
Bimal Pandey ◽  
Sanjit Karki ◽  
Roshan Shrestha ◽  
Nora Ranjitkar ◽  
Buddhi Poudyal ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Chart Review ◽  
Kidney Biopsy ◽  
Surgical Intervention ◽  
Immunoglobulin A ◽  
National Registry ◽  
Glomerular Disease ◽  
Immunoglobulin A Nephropathy ◽  
Standard Tool ◽  
Nephrotic Range Proteinuria

Introductions: Kidney biopsy is the standard tool to diagnose glomerular disease (GD). There is lack of national registry of kidney biopsy for the type, incidence and prevalence of GD. We aim to review kidney biopsy at Patan Hospital for profile of GD in local scenario. Methods: This was a chart review of patients who underwent kidney biopsy at Patan Hospital, Nepal, from October 2013 to September 2015. We analyzed the data for indication of kidney biopsy, types of GD and complication of biopsy. Results: There were 117 patients who had kidney biopsies. Immunoglobulin A Nephropathy was seen in 42 (35.8%) and Lupus Nephritis in 38 (32.5%). Sub nephrotic range proteinuria with or without active urinary sediments was found in 75 (64%). Blood transfusion was required in 3 (2.5%) patients after biopsy. There was no surgical intervention or mortality related to biopsy. Conclusions: IgA Nephropathy was the commonest glomerular disease. Kidney biopsy was a safe and effective procedure.

Role of Transforming Growth Factor-β1 in Glomerulonephritis

1997 ◽  
Vol 25 (2) ◽  
pp. 71-80 ◽  
Author(s):  
Y Taniguchi ◽  
N Yorioka ◽  
T Masaki ◽  
K Yamashita ◽  
T Ito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tissue Damage ◽  
Transforming Growth Factor ◽  
Immunoglobulin A ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Renal Tissue ◽  
Immunoglobulin A Nephropathy ◽  
Tubulointerstitial Lesions

The role of transforming growth factor-β1 (TGF-β1) in human glomerulonephritis is still poorly understood. The relationship between expression of TGF-β1 protein or TGF-β1 mRNA and tissue damage was investigated using the enzyme–antibody and in situ hybridization method in frozen slices of renal tissue from 30 patients: 25 with glomerulonephritis (18 with immunoglobulin A nephropathy; two with focal glomerulosclerosis, one with membranous nephropathy, one with crescentic glomerulonephritis and three with lupus nephritis) and five control patients with minimal change disease. The expression of TGF-β1 mRNA was high in sclerotic and proliferative glomeruli, as well as in the tubular epithelial cells within tubulointerstitial lesions. There was significant correlation between the severity of tissue damage in immunoglobulin A nephropathy and the presence of TGF-β1protein and TGF-β1 mRNA. These findings suggest that TGF-β1 is involved in glomerulosclerosis and the development of tubulointerstitial lesions, indicating its potential importance in the progression and aggravation of immunoglobulin A nephropathy.

scholarly journals Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Momoko Hamano ◽  
Seitaro Nomura ◽  
Midori Iida ◽  
Issei Komuro ◽  
Yoshihiro Yamanishi
Keyword(s):  
Heart Failure ◽  
Single Cell ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Marker Genes ◽  
Specific Gene ◽  
Rna Seq ◽  
Aortic Constriction ◽  
Multiple Risk Factors

AbstractHeart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart failure and identifying marker genes to distinguish heterogeneous phenotypes, by integrating multiple omics data including single-cell RNA-seq, ChIP-seq, and gene interactome data. We detected a significant increase in the expression level of natriuretic peptide A (Nppa), after stress loading with transverse aortic constriction (TAC), and showed that cardiomyocytes with high Nppa expression displayed specific gene expression patterns. Multiple NADH ubiquinone complex family, which are associated with the mitochondrial electron transport system, were negatively correlated with Nppa expression during the early stages of cardiac hypertrophy. Large-scale ChIP-seq data analysis showed that Nkx2-5 and Gtf2b were transcription factors characteristic of high-Nppa-expressing cardiomyocytes. Nppa expression levels may, therefore, represent a useful diagnostic marker for heart failure.

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