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Microarray studies of gene expression in circulating leukocytes in kidney diseases
David Alcorta1, Gloria Preston, William Munger
1Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, 315 MacNider Building, Chapel Hill, NC 27599-7155, USA.
Abstract:
The molecular characterization of changes in mRNA expression in renal tissue during disease is hampered by the acquisition of sufficient mRNA to do genomewide expression profiling. In many renal diseases, such as systemic lupus erythematosus, IgA nephropathy, antineutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis, and small-vessel vasculitis (ANCA disease), circulating leukocytes play a role in onset, progression, and severity of the condition. Circulating leukocytes are readily isolated and supply sufficient mRNA for analysis, allowing molecular investigation into their involvement in the disease process. Our laboratory has undertaken a systematic study of the genomewide expression profiles of the circulating leukocytes from patients with a variety of renal diseases (ANCA disease, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis), using the Affymetrix high-density gene chip array technology. Analysis of the data showed clustering of expressed genes unique for each individual disease group. These results imply that significant gene expression changes occur in leukocytes that are circulating in patients with renal diseases. In addition, gene expression has been studied in leukocytes activated in vitro by mechanisms that mimic pathogenic events in vivo. The expression levels of genes identified in in vitro studies were compared with the patient leukocyte gene expression to determine whether similar pathological events were occurring in vivo.
Insights
Gene expression profiling in circulating leukocytes offers a viable method for studying kidney diseases. This approach reveals unique molecular signatures for various renal conditions, aiding in understanding disease mechanisms.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- Renal tissue mRNA acquisition for gene expression profiling is challenging in kidney diseases.
- Circulating leukocytes are implicated in the onset, progression, and severity of many renal diseases.
- Leukocytes provide sufficient mRNA for molecular analysis, enabling investigation of their disease involvement.
Purpose of the Study:
- To investigate genomewide mRNA expression profiles in circulating leukocytes from patients with various renal diseases.
- To identify disease-specific gene expression patterns in leukocytes.
- To compare in vivo leukocyte gene expression with in vitro activated leukocytes to understand pathogenic mechanisms.
Main Methods:
- Systematic study of genomewide expression profiles using Affymetrix high-density gene chip arrays.
- Isolation and analysis of circulating leukocytes from patients with ANCA disease, IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis.
- In vitro activation of leukocytes to mimic pathogenic events and comparison with in vivo expression data.
Main Results:
- Clustering of expressed genes unique to each individual renal disease group was observed.
- Significant gene expression changes were identified in circulating leukocytes of patients with renal diseases.
- Comparison of in vitro and in vivo data suggests potential parallels in pathogenic events.
Conclusions:
- Genomewide expression profiling of circulating leukocytes is a feasible approach for characterizing molecular changes in renal diseases.
- Distinct leukocyte gene expression signatures exist for different renal conditions.
- Further research can elucidate the role of leukocyte gene expression in kidney disease pathogenesis.