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Calcium phosphate and calcium oxalate crystal handling is dependent upon CLC-5 expression in mouse collecting duct cells

Lookup NU author(s): Professor John SayerORCiD, Dr Georgina Carr, Professor Nicholas Simmons


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Defects in an intracellular chloride channel CLC-5 cause Dent's disease, an inherited kidney stone disorder. Using a collecting duct model, mIMCD-3 cells, we show expression of dimeric mCLC-5. Transient transfection of antisense CLC-5 reduces CLC-5 protein expression. Binding of both calcium phosphate (hydroxyapatite) and calcium oxalate monohydrate (COM) crystals overlaid onto mIMCD-3 cultures was affected by altered CLC-5 expression. Calcium phosphate crystal agglomerations (>10 μm) were minimal in control (9%) and sense (13%) CLC-5-transfected cells, compared to 66% of antisense CLC-5-transfected cells (P<0.001). Small calcium phosphate crystals (<10 μm) were found associated with 45% of sense CLC-5-treated cells, of which the majority (11/14 cells) appeared to be internalised within the cell. Calcium oxalate agglomerations (>10 μm) were also largely absent for controls or sense mCLC-5 transfectants (11% and 9% of cells, respectively) with COM crystal agglomerates predominating in antisense CLC-5 transfectants (66%, P<0.0001). We conclude that collecting duct cells with reduced CLC-5 expression lead to a tendency to form calcium crystal agglomeration, which may help explain the nephrocalcinosis and nephrolithiasis seen in Dent's disease. © 2004 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Sayer JA, Carr G, Simmons NL

Publication type: Article

Publication status: Published

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Year: 2004

Volume: 1689

Issue: 1

Pages: 83-90

ISSN (print): 0925-4439

ISSN (electronic): 0006-3002

Publisher: Elsevier BV


DOI: 10.1016/j.bbadis.2004.02.007

PubMed id: 15158917


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