Gene expression in early and progression phases of autosomal dominant polycystic kidney disease

Wen-Cheng Chen,Yi-Shiuan Tzeng,Hung Li

doi:10.1186/1756-0500-1-131

Abstract

BackgroundLittle is known about the genes involved in the initial cyst formation and disease progression in autosomal dominant polycystic kidney disease (ADPKD); however, such knowledge is necessary to explore therapeutic avenues for this common inherited kidney disease.FindingsTo uncover the genetic determinants and molecular mechanisms of ADPKD, we analyzed 4-point time-series DNA microarrays from Pkd1L3/L3 mice to generate high resolution gene expression profiles at different stages of disease progression. We found different characteristic gene expression signatures in the kidneys of Pkd1L3/L3 mice compared to age-matched controls during the initial phase of the disease. By postnatal week 1, the Pkd1L3/L3 kidney already had a distinctive gene expression pattern different from the corresponding normal controls.ConclusionThe genes differentially expressed, either induced or repressed, in ADPKD are important in immune defense, cell structure and motility, cellular proliferation, apoptosis and metabolic processes, and include members of three pathways (Wnt, Notch, and BMP) involved in morphogenetic signaling. Further analysis of the gene expression profiles from the early stage of cystogenesis to end stage disease identified a possible gene network involved in the pathogenesis of ADPKD.

Highlights

Little is known about the genes involved in the initial cyst formation and disease progression in autosomal dominant polycystic kidney disease (ADPKD); such knowledge is necessary to explore therapeutic avenues for this common inherited kidney disease
The genes differentially expressed, either induced or repressed, in ADPKD are important in immune defense, cell structure and motility, cellular proliferation, apoptosis and metabolic processes, and include members of three pathways (Wnt, Notch, and BMP) involved in morphogenetic signaling
Further analysis of the gene expression profiles from the early stage of cystogenesis to end stage disease identified a possible gene network involved in the pathogenesis of ADPKD

Summary

Conclusion

Comprehensive gene expression profiles from early to end stage ADPKD were generated from Pkd1L3/L3 mice, an improved disease model. Several distinct early expression signatures of differentially expressed genes with potential roles in cystogenesis were identified. These genes are involved in several pathways including cell proliferation, apoptosis, transport, and immune defenses. A variety of biochemical pathways are clearly involved in the pathogenesis of ADPKD, both in initial cystogenesis and throughout disease progression, with extensive crosstalk between different pathways. Further investigation of these genes and their associated networks may provide insight into the possible pathogenic mechanisms of ADPKD development, and identify potential diagnostic and prognostic markers and novel therapeutic targets

Findings

Results

Materials and methods

Gabow PA

Young RA