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Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
Published on: September 1, 2015
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Glucose promotes secretion-dependent renal cyst growth
Andre Kraus1, Gunnar Schley1, Karl Kunzelmann2
1Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany.
Journal of Molecular Medicine (Berlin, Germany)
|September 4, 2015
Summary
High glucose levels promote polycystic kidney disease (PKD) cyst growth by increasing calcium-activated chloride channel ANO1 expression and activity. Managing blood sugar may reduce cyst enlargement in PKD patients.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Polycystic kidney diseases (PKDs) involve bilateral renal cyst development, impairing kidney function.
- Cyst growth is driven by transepithelial chloride secretion, influenced by intracellular cAMP and calcium.
- Regulatory mechanisms of these secretory pathways in PKD are not fully understood.
Purpose of the Study:
- To investigate the impact of glucose concentration on renal tubular cell cyst growth.
- To explore the role of the calcium-activated chloride channel ANO1 in glucose-dependent cystogenesis.
- To assess the potential of inhibiting ANO1 to reduce cyst growth.
Main Methods:
- In vitro culture of renal tubular cells in a collagen matrix.
- Analysis of embryonic kidneys deficient or competent for Pkd1.
- Measurement of chloride secretion using Ussing chamber techniques.
- Assessment of ANO1 expression and localization.
Main Results:
- Glucose concentration significantly impacts renal cyst growth in both tested models.
- High glucose induces transcriptional upregulation and apical membrane expression of ANO1.
- Inhibition of ANO1 with CaCCinh-AO1 effectively reduces glucose-dependent cyst growth.
- High glucose increases apical chloride secretion, which is blocked by CaCCinh-AO1.
Conclusions:
- Renal cyst growth in PKD is significantly influenced by glucose concentration.
- High glucose promotes cyst growth via upregulation of ANO1 and subsequent chloride secretion.
- Targeting ANO1 presents a potential therapeutic strategy for managing PKD progression.
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