title: Oxalate ions and calcium oxalate crystal-induced up-regulation of osteopontin and monocyte chemoattractant protein-1 in renal fibroblasts.
abstract: OBJECTIVE
  To examine the responses of renal fibroblasts to high oxalate (Ox) and calcium Ox (CaOx) crystals, as the latter are found in the renal interstitium of patients with primary or enteric hyperoxaluria, and in animals with experimental CaOx nephrolithiasis, and are associated with tubulointerstitial inflammation (TI). TI might begin with the production of chemoattractants by the renal epithelial cells exposed to high Ox and/or CaOx crystals; as Ox levels are also high in the renal interstitium and crystal deposition in nephrolithiasis might start in the interstitium, we hypothesized that renal fibroblasts might also be involved in the development of TI.
  
  
  METHODS
  We exposed renal fibroblast cells of line NRK 49F in vitro to Ox ions (500 micromol/L) or CaOx monohydrate crystals (67 microg/cm(2)). We assessed the production of osteopontin and monocyte chemoattractant protein-1 (MCP-1), and expression of their mRNA, in the cells. We also determined the cellular malondialdehyde content as a marker of reactive oxygen species (ROS)-induced lipid peroxidation, and Trypan blue staining and the release of lactate dehydrogenase as markers of injury.
  
  
  RESULTS
  Similar to renal epithelial cells, renal fibroblasts were stimulated by exposure to Ox and CaOx crystals. They showed signs of injury and ROS-induced lipid peroxidation. The mRNA expression and production of osteopontin and MCP-1 increased significantly.
  
  
  CONCLUSIONS
  These results indicate that fibroblasts respond to high Ox and CaOx crystals by up-regulating specific pathways producing pro-inflammatory conditions. Migration of monocytes/macrophages to sites of interstitial crystal deposits can lead to localized interstitial inflammation and fibrosis.
authors.affiliation: Department of Urology, Kinki University, School of Medicine, Osaka, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Umekawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Iguchi
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D003460:Crystallization; D005347:Fibroblasts / Q000378:metabolism; D007477:Ions; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D053495:Osteopontin; D010070:Oxalates / Q000378:metabolism*; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D007477:Ions; D010070:Oxalates; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D002129:Calcium Oxalate