Document Detail


The initial and subsequent inflammatory events during calcium oxalate lithiasis.
MedLine Citation:
PMID:  20347754     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Crystallization is believed to be the initiation step of urolithiasis, even though it is unknown where inside the nephron the first crystal nucleation occurs. METHODS: Direct nucleation of calcium oxalate and subsequent events including crystal retention, cellular damage, endocytosis, and hyaluronan (HA) expression, were tested in a two-compartment culture system with intact human proximal tubular HK-2 cell monolayer. RESULTS: Calcium oxalate dihydrate (COD) was nucleated and bound onto the apical surface of the HK-2 cells under hypercalciuric and hyperoxaluric conditions. These cells displayed mild cellular damage and internalized some of the adhered crystals within 18h post-COD-exposure, as revealed by electron microscopy. Prolonged incubation in complete medium caused significant damage to disrupt the monolayer integrity. Furthermore, hyaluronan disaccharides were detected in the harvested media, and were associated with HAS-3 mRNA expression. CONCLUSION: Human proximal cells were able to internalize COD crystals which nucleated directly onto the apical surface, subsequently triggering cellular damage and HAS-3 specific hyaluronan synthesis as an inflammatory response. The proximal tubule cells here demonstrate that it plays an important role in facilitating urolithiasis via endocytosis and creating an inflammatory environment whereby free hyaluronan in tubular fluid can act as crystal-binding molecule at the later segments of distal and collecting tubules.
Authors:
John W M Yuen; Mayur-Danny I Gohel; Ngork-Wah Poon; Daisy K Y Shum; Po-Chor Tam; Doris W T Au
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-27
Journal Detail:
Title:  Clinica chimica acta; international journal of clinical chemistry     Volume:  411     ISSN:  1873-3492     ISO Abbreviation:  Clin. Chim. Acta     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-09-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1302422     Medline TA:  Clin Chim Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1018-26     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Health Technology & Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Biological Transport
Calcium / pharmacology
Calcium Oxalate / chemistry,  metabolism*,  pharmacology
Cell Line
Epithelial Cells / drug effects,  metabolism,  pathology
Gene Expression Regulation / drug effects
Glucuronosyltransferase / genetics
Humans
Inflammation / genetics,  metabolism,  pathology
Kidney Tubules, Proximal / pathology
Lithiasis / genetics,  metabolism*,  pathology
Chemical
Reg. No./Substance:
25454-23-3/Calcium Oxalate; 7440-70-2/Calcium; EC 2.4.1.-/HAS3 protein, human; EC 2.4.1.17/Glucuronosyltransferase

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