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Published on: November 25, 2015
ADPKD cell proliferation and Cl--dependent fluid secretion
Gail A Reif1, Darren P Wallace1
1Departments of Internal Medicine and Molecular and Integrative Physiology, and The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, KS, United States.
Insights
Autosomal dominant polycystic kidney disease (ADPKD) involves cyst growth driven by cell proliferation and fluid secretion. This study details methods to measure these processes for developing new ADPKD therapies.
Area of Science:
- Nephrology
- Genetics
- Cell Biology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic kidney disorder.
- It causes cyst formation, inflammation, fibrosis, and kidney function decline.
- The precise mechanisms of cystogenesis in ADPKD are not fully understood.
Purpose of the Study:
- To explore cellular and molecular mechanisms of ADPKD cyst epithelial cell proliferation.
- To investigate mechanisms of chloride-dependent fluid secretion in ADPKD.
- To evaluate potential therapeutic strategies targeting cyst growth pathways.
Main Methods:
- Utilizing in vitro assays to study ADPKD cyst epithelial cells.
- Measuring ADPKD cell proliferation rates.
- Quantifying transepithelial chloride secretion and net fluid transport.
Main Results:
- Established methods for assessing key ADPKD cyst growth drivers.
- Provided a framework for evaluating therapeutic interventions in controlled experimental settings.
- Highlighted the roles of cell proliferation and fluid secretion in ADPKD pathogenesis.
Conclusions:
- In vitro assays are crucial for understanding ADPKD mechanisms.
- These methods facilitate the evaluation of novel therapeutic targets.
- Further research using these assays can advance ADPKD treatment strategies.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by bilateral fluid-filled cysts, renal inflammation and extensive fibrosis, leading to the progressive decline in kidney function. Renal cyst formation begins in utero from aberrant proliferation of tubule epithelial cells; however, the mechanisms for cystogenesis remain unclear. Cell proliferation and Cl--dependent fluid secretion, which drives the accumulation of cyst fluid, are responsible for inexorable growth of cysts and the remarkable appearance of massively enlarged ADPKD kidneys. Investigators have used in vitro assays to explore cellular and molecular mechanisms involved in ADPKD cyst epithelial cell proliferation and Cl--dependent fluid secretion in experimentally controlled environments. These assays have been used to evaluate potential therapeutic approaches to inhibit cellular pathways involved in cyst growth. This chapter discusses methods for measuring ADPKD cell proliferation, transepithelial Cl- secretion, and net fluid transport across cyst epithelial cell monolayers.
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