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A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease
- Source :
- Chi, T; Kim, MS; Lang, S; Bose, N; Kahn, A; Flechner, L; et al.(2015). A Drosophila model identifies a critical role for zinc in mineralization for kidney stone disease. PLoS ONE, 10(5). doi: 10.1371/journal.pone.0124150. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/9sn8r52g, PloS one, vol 10, iss 5, PLoS ONE, Vol 10, Iss 5, p e0124150 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- © 2015 Chi et al. Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall's plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.
- Subjects :
- Kidney Disease
Xanthine Dehydrogenase
lcsh:Medicine
Gene Expression
Kidney
Ectopic calcification
Drosophila Proteins
2.1 Biological and endogenous factors
RNA, Small Interfering
Aetiology
lcsh:Science
Cation Transport Proteins
Chelating Agents
Multidisciplinary
Ethylenediamines
3. Good health
Zinc
Drosophila melanogaster
X-Ray Absorption Spectroscopy
medicine.anatomical_structure
Renal and Urogenital
Dietary Proteins
Drosophila Protein
Research Article
medicine.drug
Urologic Diseases
medicine.medical_specialty
General Science & Technology
Allopurinol
1.1 Normal biological development and functioning
Malpighian Tubules
Biology
Small Interfering
Kidney Calculi
Dogs
Underpinning research
Internal medicine
medicine
Animals
Humans
Nutrition
Animal
lcsh:R
Kidney metabolism
medicine.disease
Disease Models, Animal
Endocrinology
Kidney stone disease
Disease Models
RNA
lcsh:Q
Kidney stones
Calcification
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....ddefef0cab7008ea8e681e0a2e4a9ddd