Related Experiment Video
Updated: Jul 12, 2026
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
New insights into ADPKD molecular pathways using combination of SAGE and microarray technologies
Hervé Husson1, Partha Manavalan, Viatcheslav R Akmaev
1Functional Genomics, Genzyme Corporation, Framingham, MA 01701-9322, USA.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene, but cellular mechanisms of cystogenesis remain unclear. In an attempt to display the array of cyst-specific molecules and to elucidate the disease pathway, we have performed comprehensive high-throughput expression analysis of normal and ADPKD epithelia in a two-step fashion. First, we generated expression profiles of normal and cystic epithelia derived from kidney and liver using serial analysis of gene expression (SAGE). We found 472 and 499 differentially expressed genes with fivefold difference in liver and kidney libraries, respectively. These genes encode growth factors, transcription factors, proteases, apoptotic factors, molecules involved in cell-extracellular matrix interactions, and ion channels. As a second step, we constructed a custom cDNA microarray using a subset of the differentially regulated genes identified by SAGE and interrogated ADPKD patient samples. Subsequently, a set of differentially expressed genes was refined to 26 up-regulated and 48 down-regulated genes with ap value of <0.01. This study may provide valuable insights into the pathophysiology of ADPKD and suggest potential therapeutic targets.
Insights
This study identifies key genes involved in autosomal dominant polycystic kidney disease (ADPKD) cyst formation using gene expression analysis. Findings reveal novel molecular players and potential therapeutic targets for ADPKD.
Area of Science:
- Genetics
- Molecular Biology
- Nephrology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by cyst formation in the kidneys and liver.
- The precise cellular mechanisms driving ADPKD cystogenesis are not fully understood.
- Mutations in PKD1 or PKD2 genes are the primary cause of ADPKD.
Purpose of the Study:
- To identify cyst-specific molecules and elucidate the disease pathway in ADPKD.
- To comprehensively analyze gene expression profiles in normal versus ADPKD epithelia.
- To discover potential therapeutic targets for ADPKD.
Main Methods:
- Utilized serial analysis of gene expression (SAGE) to profile gene expression in normal and ADPKD kidney and liver epithelia.
- Developed a custom cDNA microarray based on SAGE-identified differentially expressed genes.
- Interrogated ADPKD patient samples using the custom microarray for further gene expression analysis.
Main Results:
- Identified 472 and 499 differentially expressed genes in liver and kidney ADPKD epithelia, respectively, with a fivefold difference.
- Genes identified are involved in growth factors, transcription, proteolysis, apoptosis, cell-matrix interactions, and ion channels.
- Refined the gene set to 26 up-regulated and 48 down-regulated genes (p<0.01) in ADPKD patients.
Conclusions:
- The study provides significant insights into the molecular pathophysiology of ADPKD.
- The identified differentially expressed genes represent potential targets for future ADPKD therapies.
- This research advances the understanding of cystogenesis in ADPKD.
