Glucose promotes secretion-dependent renal cyst growth.

Abstract

UNLABELLED:

Polycystic kidney diseases are characterized by the development of numerous bilateral renal cysts that continuously enlarge resulting in a decline of kidney function due to compression of intact nephrons. Cyst growth is driven by transepithelial chloride secretion which depends on both intracellular cAMP and calcium. Mechanisms that are involved in the regulation of the underlying secretory pathways remain incompletely understood. Here we show that glucose concentration has a strong impact on cyst growth of renal tubular cells within a collagen matrix as well as in embryonic kidneys deficient or competent for Pkd1. Glucose-dependent cyst growth correlates with the transcriptional induction of the calcium-activated chloride channel anoctamin 1 (ANO1) and its increased expression in the apical membrane of cyst-forming cells. Inhibition of ANO1 with the specific inhibitor CaCCinh-AO1 significantly decreases glucose-dependent cyst growth in both models. Ussing chamber analyses revealed increased apical chloride secretion of renal tubular cells upon exposure to high glucose medium which can also be inhibited by the use of CaCCinh-AO1. These data suggest that glycemic control may help to reduce renal cyst growth in patients with polycystic kidney disease.

KEY MESSAGE:

Renal cyst growth depends on glucose concentration in two in vitro cyst models. High glucose leads to upregulation of the calcium-activated chloride channel ANO1. High glucose promotes calcium-activated chloride secretion via ANO1. Glucose-dependent secretion can be inhibited by a specific inhibitor of ANO1.

• Authors: Andre Kraus, Gunnar Schley, Karl Kunzelmann, Rainer Schreiber, Dorien J M Peters, Ruth Stadler, Kai-Uwe Eckardt, Bjoern Buchholz
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 94 Issue 1 Pg. 107-17 (Jan 2016) ISSN: 1432-1440 [Electronic] Germany
• PMID: 26334260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANO1 protein, mouse
• Anoctamin-1
• Chloride Channels
• Chlorides
• TRPP Cation Channels
• polycystic kidney disease 1 protein
• Cyclic AMP
• Glucose
• Calcium

Topics

• Animals
• Anoctamin-1
• Calcium (metabolism)
• Cell Line
• Cell Proliferation (drug effects)
• Chloride Channels (antagonists & inhibitors, biosynthesis, genetics)
• Chlorides (metabolism)
• Cyclic AMP (metabolism)
• Cysts (pathology)
• Dogs
• Glucose (pharmacology)
• Kidney Tubules (cytology, embryology, pathology)
• Madin Darby Canine Kidney Cells
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Polycystic Kidney, Autosomal Dominant (pathology)
• TRPP Cation Channels (genetics)
• Transcriptional Activation (genetics)