Gene profiling of polycystic kidneys

Schieren, Gisela; Rumberger, Brigitta; Klein, Marinella; Kreutz, Clemens; Wilpert, Jochen; Geyer, Marcel; Faller, Daniel; Timmer, Jens; Quack, Ivo; Rump, Lars Christian; Walz, Gerd; Donauer, Johannes

doi:10.1093/ndt/gfl071

Cited by 62 publications

(52 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement, this reduction is negatively correlated with the height-adjusted total kidney volume of respective individuals. Interestingly, peptides from fibrinogen alpha chain and keratin are more abundant in ADPKD samples, which is in agreement with the observations that fibronectin and keratin 19 accelerate renal cystogenesis and are associated with ADPKD (Mrug et al 2008;Schieren et al 2006).…”

Section: Adpkd Biomarkerssupporting

confidence: 90%

Insights into autosomal dominant polycystic kidney disease by quantitative mass spectrometry-based proteomics

Diedrich

Dengjel

2017

Cell Tissue Res

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PKD1 and PKD2 encoding polycystin-1 and polycystin-2, respectively. Polycystin-1 and -2 form a complex, interact with several proteins involved in signal transduction and localize to discrete subcellular positions, most importantly the primary cilium. Whereas the causative mutations leading to ADPKD are known, the underlying deregulated cellular pathways are not well understood. In the current review, we introduce state-of-the-art mass spectrometry (MS)-based proteomic techniques and summarize their use in kidney and ADPKD research. Proteomic profiling approaches, the elucidation of ADPKD-relevant proteinprotein interactions and the regulation of posttranslational modifications are included. We also discuss the use of MS-based methods for ADPKD prognosis, diagnosis and disease monitoring by using protein-and peptide-based biomarkers.

show abstract

Section: Adpkd Biomarkerssupporting

confidence: 90%

Insights into autosomal dominant polycystic kidney disease by quantitative mass spectrometry-based proteomics

Diedrich

Dengjel

2017

Cell Tissue Res

View full text Add to dashboard Cite

show abstract

“…18,19 To examine the extent of renal fibrosis, we assessed collagen deposition by Masson trichrome staining. As shown in Figure 2A, kidneys from Pkd1 cond/cond :Nestin cre but not wild-type animals exhibited extensive deposition of collagen.…”

Section: Pkd1mentioning

confidence: 99%

“…Renal myofibroblasts are believed to arise from epithelial-tomesenchymal transition in PKD and contribute to the observed collagen deposition and fibrosis. 18,19 To test whether renal myofibroblasts also may play a role in our Pkd1 cond/cond :Nestin cre model, we immunostained kidney sections for smooth muscle actin (SMA). In wild-type kidneys, SMA is expressed at high levels only in the renal vascular bundles (Figure 2, B and C).…”

Section: Pkd1mentioning

confidence: 99%

Rapamycin Ameliorates PKD Resulting from Conditional Inactivation of Pkd1

Shillingford¹,

Piontek²,

Germino³

et al. 2010

Journal of the American Society of Nephrology

238

206

View full text Add to dashboard Cite

Aberrant activation of the mammalian target of rapamycin (mTOR) pathway occurs in polycystic kidney disease (PKD). mTOR inhibitors, such as rapamycin, are highly effective in several rodent models of PKD, but these models result from mutations in genes other than Pkd1 and Pkd2, which are the primary genes responsible for human autosomal dominant PKD. To address this limitation, we tested the efficacy of rapamycin in a mouse model that results from conditional inactivation of Pkd1. Mosaic deletion of Pkd1 resulted in PKD and replicated characteristic features of human PKD including aberrant mTOR activation, epithelial proliferation and apoptosis, and progressive fibrosis. Treatment with rapamycin was highly effective: It reduced cyst growth, preserved renal function, inhibited epithelial cell proliferation, increased apoptosis of cyst-lining cells, and inhibited fibrosis. These data provide in vivo evidence that rapamycin is effective in a human-orthologous mouse model of PKD.

show abstract

“…The maturity of the technology, its low cost, the availability of data analysis programs (such as gene ontology analysis 1 or gene set enrichment analysis 2 ), and the presence of institutional microarray core facilities have made such analyses relatively straightforward. This technology is increasingly used in kidney research, for example to identify the transcriptional circuitry of polycystic kidney disease modifiers, 3 to distinguish polycystic kidney disease profiles with that of allograft nephropathy, 4 and to analyze the transcriptome in ischemia-reperfusion injury [5][6][7] and in renal fibrosis. 8,9 The Genitourinary Database Molecular Anatomy Project (GudMap) serves as a repository for gene expression datasets in developing and adult kidneys.…”

mentioning

confidence: 99%

Translational Profiles of Medullary Myofibroblasts during Kidney Fibrosis

Grgic

Krautzberger

Hofmeister

et al. 2014

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Myofibroblasts secrete matrix during chronic injury, and their ablation ameliorates fibrosis. Development of new biomarkers and therapies for CKD will be aided by a detailed analysis of myofibroblast gene expression during the early stages of fibrosis. However, dissociating myofibroblasts from fibrotic kidney is challenging. We therefore adapted translational ribosome affinity purification (TRAP) to isolate and profile mRNA from myofibroblasts and their precursors during kidney fibrosis. We generated and characterized a transgenic mouse expressing an enhanced green fluorescent protein (eGFP)-tagged L10a ribosomal subunit protein under control of the collagen1a1 promoter. We developed a one-step procedure for isolation of polysomal RNA from collagen1a1-eGFPL10a mice subject to unilateral ureteral obstruction and analyzed and validated the resulting transcriptional profiles. Pathway analysis revealed strong gene signatures for cell proliferation, migration, and shape change. Numerous novel genes and candidate biomarkers were upregulated during fibrosis, specifically in myofibroblasts, and we validated these results by quantitative PCR, in situ, and Western blot analysis. This study provides a comprehensive analysis of early myofibroblast gene expression during kidney fibrosis and introduces a new technique for cell-specific polysomal mRNA isolation in kidney injury models that is suited for RNA-sequencing technologies.

show abstract

Gene profiling of polycystic kidneys

Abstract: Our results show that the end stage of ADPKD is associated with increased markers of EMT, suggesting that EMT contributes to the progressive loss of renal function in ADPKD.

Cited by 62 publications

References 18 publications

Insights into autosomal dominant polycystic kidney disease by quantitative mass spectrometry-based proteomics

Insights into autosomal dominant polycystic kidney disease by quantitative mass spectrometry-based proteomics

Rapamycin Ameliorates PKD Resulting from Conditional Inactivation of Pkd1

Translational Profiles of Medullary Myofibroblasts during Kidney Fibrosis

Contact Info

Product

Resources

About