The Gene Expression Profile of Cyst Epithelial Cells in Autosomal Dominant Polycystic Kidney Disease Patients

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the formation of fluid-filled cysts in the kidney and progressive renal failure. Other manifestations of ADPKD include the formation of cysts in other organs (liver, pancreas, and spleen), hypertension, cardiac defects, and cerebral aneurysms. The loss of function of the polycystin -1 and -2 results in the formation of epithelium-lined cysts, a process that depends on initial epithelial proliferation. cDNA microarrays powerfully monitor gene expression and have led to the discoveries of pathways regulating complex biological processes. We undertook to profile the gene expression patterns of epithelial cells derived from the cysts of ADPKD patients using the cDNA microarray technique. Candidate genes that were differently expressed in cyst tissues were identified. 19 genes were up-regulated, and 6 down-regulated. Semi-quantitative RT-PCR results were consistent with the microarray findings. To distinguish between normal and epithelial cells, we used the hierarchical method. The results obtained may provide a molecular basis for understanding the biological meaning of cytogenesis.

Aquaporin‐11 knockout mice and polycystic kidney disease animals share a common mechanism of cyst formation

“…Comparing our results with those of the transcriptomal analysis of ADPKD patients reported by Schieren et al (49), only 23 of the 85 genes that they selected demonstrated a regulation pattern similar to those of the genes analyzed in our study. In the case of the transcriptomal analysis of cultured cells derived from ADPKD patients by Lee et al (50), as few as 7 of the 52 genes selected showed a regulation pattern similar to that of the genes analyzed by us; moreover, 12 genes demonstrated opposite regulation. In addition, Mmp12 that was observed to be greatly up‐regulated (23.87‐fold) in the kidneys of Aqp11 –/– mice in our study (Fig.…”

Sustained cell proliferation of renal epithelial cells in mice with inv mutation

“…Kidney samples for lectin staining were frozen in liquid nitrogen into Tissue Tek OCT compound (Miles; Elkhart, IN, USA) and stored at −70 °C until sectioned. Sections Table 2 Comparison of renal mRNA expression among inv∆C mice in the present study, pcy mice (Nakamura et al 1993;Gattone et al 1996), human ADPKD cells (Husson et al 2004;Lee et al 2004) and cpk mice (Gattone et al 2002) were performed at 10 µm, and fixed in 4% PFA in 0.1 m phosphate buffer, pH 7.5 at room temperature for 20 min. FITC conjugated LTA and rhodamine conjugated DBA were used at a concentration of 50-100 µg/mL in PBS.…”

Monozygotic Twins With Mirror Image Cysts: Indication of a Genetic Mechanism in Arachnoid Cysts?

“…1 In ADPKD, arachnoid cysts have been reported to co-exist. 2 The observations of familial occurrence of arachnoid cysts, 2,3 in combination with the observed co-existence of arachnoid cysts and genetically determined cystic diseases, 2,3 indicate a genetic component in the cystogenesis of at least some of the arachnoid cysts.…”