Kraus, Andre and Schley, Gunnar and Kunzelmann, Karl and Schreiber, Rainer and Peters, Dorien J. M. and Stadler, Ruth and Eckardt, Kai-Uwe and Buchholz, Bjoern (2016) Glucose promotes secretion-dependent renal cyst growth. JOURNAL OF MOLECULAR MEDICINE-JMM, 94 (1). pp. 107-117. ISSN 0946-2716, 1432-1440
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLYCYSTIC KIDNEY-DISEASE; ACTIVATED CHLORIDE SECRETION; EPITHELIAL-CELLS; CL-SECRETION; CFTR; CAMP; CA2+; PROLIFERATION; CYSTOGENESIS; METABOLISM; Polycystic kidney disease; Cyst growth; Chloride secretion; Glucose; Diabetes mellitus type 2; Anoctamin 1 |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Mar 2019 12:36 |
| Last Modified: | 07 Mar 2019 10:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2237 |
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