Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptomic and proteomic profiling reveal insights of mesangial cell function in patients with IgA Nephropathy

ABSTRACT: IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN. RNA from glomerular compartment was extracted and processed for hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.

ORGANISM(S): Homo sapiens

SUBMITTER: Celine Berthier

PROVIDER: E-GEOD-93798 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.

Liu Peidi P Lassén Emelie E Nair Viji V Berthier Celine C CC Suguro Miyuki M Sihlbom Carina C Kretzler Matthias M Betsholtz Christer C Haraldsson Börje B Ju Wenjun W Ebefors Kerstin K Nyström Jenny J

Journal of the American Society of Nephrology : JASN 20170623 10

IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene e ...[more]

PMID: 28646076

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Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN) RNA from tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix HG-U133A microarrays.

Dataset Information

Transcriptomic and proteomic profiling reveal insights of mesangial cell function in patients with IgA Nephropathy

Publications

Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.

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