title: Calcium oxalate nephrolithiasis and expression of matrix GLA protein in the kidneys.
abstract: OBJECTIVE
  Polymorphism of the gene for matrix GLA protein (MGP), a calcification inhibitor, is associated with nephrolithiasis. However, experimental investigations of MGP role in stone pathogenesis are limited. We determined the effect of renal epithelial exposure to oxalate (Ox), calcium oxalate (CaOx) monohydrate (COM) or hydroxyapatite (HA) crystal on the expression of MGP.
  
  
  METHODS
  MDCK cells in culture were exposed to 0.3, 0.5 or 1 mM Ox and 33, 66 or 133-150 μg/cm(2) of COM/HA for 3-72 h. MGP expression and production were determined by Western blotting and densitometric analysis. Enzyme-linked immunosorbent assay was performed to determine MGP release into the medium. Hyperoxaluria was induced in male Sprague-Dawley rats by feeding hydroxyl-L-proline. Immunohistochemistry was performed to detect renal MGP expression.
  
  
  RESULTS
  Exposure to Ox and crystals led to time- and concentration-dependent increase in expression of MGP in MDCK cells. Cellular response was quicker to crystal exposure than to the Ox, expression being significantly higher after 3-h exposure to COM or HA crystals and more than 6 h of exposure to Ox. MGP expression was increased in kidneys of hyperoxaluric rats particularly in renal peritubular vessels.
  
  
  CONCLUSIONS
  We demonstrate increased expression of MGP in renal tubular epithelial cells exposed to Ox or CaOx crystals as well as the HA crystals. The most significant finding of this study is the increased staining seen in renal peritubular vessels of the hyperoxaluric rats, indicating involvement of renal endothelial cells in the synthesis of MGP.
authors.affiliation: Department of Pathology, Immunology & Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, USA.
authors.forename: Aslam
authors.initials: A
authors.lastname: Khan
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000009:adverse effects* / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017886:Durapatite / Q000009:adverse effects / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006909:Hydroxyproline / Q000009:adverse effects; D006959:Hyperoxaluria / Q000139:chemically induced / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D053040:Nephrolithiasis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D010070:Oxalates / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000097568:Matrix Gla Protein
chemical_list: D002129:Calcium Oxalate; D002135:Calcium-Binding Proteins; D017886:Durapatite; D016326:Extracellular Matrix Proteins; D006909:Hydroxyproline; D010070:Oxalates; D000097568:Matrix Gla Protein