scholarly journals Role of obstruction in autosomal dominant polycystic kidney disease in rats

1996 ◽  
Vol 50 (3) ◽  
pp. 873-886 ◽  
Author(s):  
George A. Tanner ◽  
Norbert Gretz ◽  
Bret A. Connors ◽  
Andrew P. Evan ◽  
Michael Steinhausen
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Molecular Pathways and Therapies in Autosomal-Dominant Polycystic Kidney Disease

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 195-207 ◽  
Author(s):  
Takamitsu Saigusa ◽  
P. Darwin Bell
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Primary Cilia ◽  
Autosomal Dominant ◽  
Molecular Pathways ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Multiple Cysts ◽  
Review Current

Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited renal disease, characterized by multiple cysts that can eventually lead to kidney failure. Studies investigating the role of primary cilia and polycystins have significantly advanced our understanding of the pathogenesis of PKD. This review will present clinical and basic aspects of ADPKD, review current concepts of PKD pathogenesis, evaluate potential therapeutic targets, and highlight challenges for future clinical studies.

scholarly journals Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

2013 ◽  
Vol 305 (6) ◽  
pp. F797-F812 ◽  
Author(s):  
Gustavo Blanco ◽  
Darren P. Wallace
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Signal Transducer ◽  
Polycystic Kidney ◽  
Cell Functions ◽  
Cell Energy ◽  
High Concentrations ◽  
Autosomal Dominant Polycystic Kidney

The classic role of the Na-K-ATPase is that of a primary active transporter that utilizes cell energy to establish and maintain transmembrane Na+ and K+ gradients to preserve cell osmotic stability, support cell excitability, and drive secondary active transport. Recent studies have revealed that Na-K-ATPase located within cholesterol-containing lipid rafts serves as a receptor for cardiotonic steroids, including ouabain. Traditionally, ouabain was viewed as a toxin produced only in plants, and it was used in relatively high concentrations to experimentally block the pumping action of the Na-K-ATPase. However, the new and unexpected role of the Na-K-ATPase as a signal transducer revealed a novel facet for ouabain in the regulation of a myriad of cell functions, including cell proliferation, hypertrophy, apoptosis, mobility, and metabolism. The seminal discovery that ouabain is endogenously produced in mammals and circulates in plasma has fueled the interest in this endogenous molecule as a potentially important hormone in normal physiology and disease. In this article, we review the role of the Na-K-ATPase as an ion transporter in the kidney, the experimental evidence for ouabain as a circulating hormone, the function of the Na-K-ATPase as a signal transducer that mediates ouabain's effects, and novel results for ouabain-induced Na-K-ATPase signaling in cystogenesis of autosomal dominant polycystic kidney disease.

Evolving role of genetic testing for the clinical management of autosomal dominant polycystic kidney disease

2018 ◽  
Vol 34 (9) ◽  
pp. 1453-1460 ◽  
Author(s):  
Matthew B Lanktree ◽  
Ioan-Andrei Iliuta ◽  
Amirreza Haghighi ◽  
Xuewen Song ◽  
York Pei
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Mutation Screening ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by mutations of two genes, PKD1 and PKD2. In the presence of a positive family history of ADPKD, genetic testing is currently seldom indicated as the diagnosis is mostly based on imaging studies using well-established criteria. Moreover, PKD1 mutation screening is technically challenging due to its large size, complexity (i.e. presence of six pseudogenes with high levels of DNA sequence similarity) and extensive allelic heterogeneity. Despite these limitations, recent studies have delineated a strong genotype–phenotype correlation in ADPKD and begun to unravel the role of genetics underlying cases with atypical phenotypes. Furthermore, adaptation of next-generation sequencing (NGS) to clinical PKD genetic testing will provide a high-throughput, accurate and comprehensive screen of multiple cystic disease and modifier genes at a reduced cost. In this review, we discuss the evolving indications of genetic testing in ADPKD and how NGS-based screening promises to yield clinically important prognostic information for both typical as well as unusual genetic (e.g. allelic or genic interactions, somatic mosaicism, cystic kidney disease modifiers) cases to advance personalized medicine in the era of novel therapeutics for ADPKD.

scholarly journals Role of the Matrix in Autosomal Dominant Polycystic Kidney Disease

Renal Failure ◽  
1998 ◽  
Vol 20 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Frank A. Carone ◽  
Robert Bacallao ◽  
Yashpal Kanwar
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
The Matrix ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Examining the Role of HIPPO/YAP and AMOT Dysregulation and Imbalance in Autosomal Dominant Polycystic Kidney Disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
John Underwood ◽  
Robert L. Bacallao
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Ectopic Expression ◽  
Renal Dialysis ◽  
National Institutes Of Health ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder, most commonly caused by mutations in Polycystin-1 and Polycystin-2 (PC1 and PC2), in which many large lumenal cysts develop in the kidney epithelium. The disease is progressive and ultimately leads to renal dialysis and/or kidney transplant given the lack of efficacious therapeutic intervention. Current research has implicated HIPPO/YAP pathway dysregulation and AMOT imbalance following defects in cell-cell adhesion and contact inhibition as the molecular basis for ADPKD. To test this hypothesis as to the minimum cellular changes necessary to produce cystogenesis, the Bacallao lab microinjected normal human kidney epithelial (HK2) cells in order to drive ectopic expression of Cadherin-8 (CAD-8). Our Imaging with confocal microscopy and subsequent image analysis indicates CAD-8, a cadherin abnormally expressed in renal epithelial cells of ADPKD patients, is sufficient to cause formation of cysts albeit with uncharacteristically small lumens compared to typical ADPKD cysts. However, these cells exhibit significantly larger cyst expansion when they are transduced for coexpression of CAD-8 and constitutively active YAP5SA. Cells modified for heterozygosity with respect to a defective PC1 gene (PKD) also exhibited significantly larger lumen cysts when transduced with YAP5SA reinforcing the role of Yap in lumen size control. Finally, PKD cells transduced with AMOTL1 exhibited significantly smaller lumen sizes. AMOTL1 belongs to a family of adapter proteins which bind and inhibit Yap activity thus showing conclusively that positive and negative modulation of Yap activity correlates with cyst lumen size expansion and reduction respectively. “This project was funded, in part, with support from the O’Brien Center for Advanced Renal Microscopic Analysis funded, in part by P30 DK079312 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

scholarly journals Is There a Role of ADAMTS-1 in Cyst Development in Autosomal Dominant Polycystic Kidney Disease?

2021 ◽  
Vol 30 (1) ◽  
pp. 25-29
Author(s):  
Suleyman Karakose ◽  
◽  
Pervin Ozkan Kurtgoz ◽  
Cigdem Damla Deniz ◽  
Edip Erkus ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Development

Role of the polycystins as mechanosensors of extracellular stiffness

2021 ◽  
Vol 320 (5) ◽  
pp. F693-F705
Author(s):  
Elisa A. Nigro ◽  
Alessandra Boletta
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Large Body ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Actomyosin Contraction ◽  
Mechanistic View

Polycystin-1 has recently emerged as a possible receptor able to sense extracellular stiffness and to negatively control the cellular actomyosin contraction machinery. Here, we revisit a large body of literature on autosomal dominant polycystic kidney disease providing a new possible mechanistic view on the topic.

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