Interaction between Osteopontin on Madin Darby Canine Kidney Cell Membrane and Calcium Oxalate Crystal

Yamate, Takanori; Kohri, Kenjiro; Umekawa, Tohru; Konya, Eiji; Ishikawa, Yasuaki; Iguchi, Masanori; Kaburagi, Takashi

doi:10.1159/000030363

Cited by 41 publications

(24 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In normal kidneys, this layer is only faintly visible and restricted to only specific locations (5,6,19), but in hyperoxaluric rats, this layer becomes very conspicuous and CaOx crystals are universally found associated with OPN (19). Pretreatment of MDCK cells with polyclonal antibodies against OPN inhibited the adhesion of CaOx crystals (40,41). Similarly, transfection of NRK52E cells with antisense OPN cDNA significantly reduced adhesion of CaOx crystals to the transfected cell (41).…”

Section: Discussionmentioning

confidence: 98%

Effect of Angiotensin II Receptor Blockage on Osteopontin Expression and Calcium Oxalate Crystal Deposition in Rat Kidneys

Umekawa¹,

Hatanaka²,

Kaburagi³

et al. 2004

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Abstract. Hyperoxaluria leads to calcium oxalate (CaOx) crystallization and development of tubulointerstitial lesions in the kidneys. Treatment of hyperoxaluric rats with angiotensin II (Ang II) type I receptor blocker (ARB) reduces lesion formation. Because Ang II mediates osteopontin (OPN) synthesis, which is involved in both macrophage recruitment and CaOx crystallization, it was hypothesized that ARB acts via OPN. Hyperoxaluria was induced in 10-wk-old male Sprague-Dawley rats, and they were treated with ARB candesartan. At the end of 4 wk, kidneys were examined for crystal deposits, ED-1-positive cells, and expression of OPN mRNA. PCR was used to quantify OPN, renin, and angiotensin-converting enzyme (ACE) mRNA in kidneys. RIA was used to determine renal, plasma, and urinary OPN; plasma renin; Ang II and ACE; and renal Ang II. For evaluating oxidative stress, malondialdehyde was measured. Urinary calcium, oxalate, creatinine, and albumin were also determined. Despite similar urinary calcium and oxalate levels, kidneys of hyperoxaluric rats on candesartan had fewer CaOx crystals, fewer ED-1-positive cells, reduced OPN expression, and reduced malondialdehyde than hyperoxaluric rats. Urinary albumin excretion and serum creatinine levels improved significantly on candesartan treatment. mRNA for OPN, renin, and ACE were significantly elevated in hyperoxaluric rats. OPN synthesis and production increased with hyperoxaluria but to a lesser extent in candesartan-treated hyperoxaluric rats. These results show for the first time that oxalate can activate the renal renin-angiotensin system and that oxalate-induced upregulation of OPN is in part mediated via renal renin-angiotensin system.Oxalate, a by-product of metabolism, is normally excreted in the urine and at low concentrations is harmless to the renal epithelial cells. However, elevated oxalate levels and/or calcium oxalate (CaOx) crystals are injurious (1-3). In addition, exposure of renal epithelial cells in vitro to high levels of oxalate and/or CaOx crystals upregulates the production of chemoattractants osteopontin (OPN) (4) and monocyte-chemoattractant protein-1 (MCP-1) (5, 6). Mild idiopathic hyperoxaluria is associated with CaOx nephrolithiasis, whereas hyperoxaluria resulting from jejunal bypass for obesity or genetic defects in oxalate metabolism is nephrotoxic and produces tubulointerstitial lesions. Tubulointerstitial damage is recognized as one of the most important risk factors for the development of chronic renal diseases and eventual renal failure (7).All components of the renin-angiotensin system (RAS) are produced within the kidney, and intrarenal RAS plays pivotal role in renal disease progression (8). Kidneys produce both angiotensinogen and angiotensin-converting enzyme (ACE), and juxtaglomerular apparatus is the main source of circulating renin. Renin catalyzes the production of angiotensin I, which is converted to angiotensin II (Ang II) by the actions of ACE. Ang II acts through two receptors, types 1 (AT1) and 2 (AT2), and mediates many ...

show abstract

Section: Discussionmentioning

confidence: 98%

Effect of Angiotensin II Receptor Blockage on Osteopontin Expression and Calcium Oxalate Crystal Deposition in Rat Kidneys

Umekawa¹,

Hatanaka²,

Kaburagi³

et al. 2004

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is possible that under these conditions sialic acid residues are exposed in a configuration that permits crystal attachment [2, 40]or that the cells express nucleonin-like calcium-binding proteins [41]. Another possibility is that these CBMs are ‘sticky’ extracellular matrix molecules, such as laminin, collagen IV [42], fibronectin, or osteopontin [43], molecules that normally are restricted to the basolateral membrane. A schematic summary of CBM expression by MDCK-I and LLC-PK 1 cells is depicted in figure 4.…”

Section: Discussionmentioning

confidence: 99%

Pericellular Matrix Formation by Renal Tubule Epithelial Cells in Relation to Crystal Binding

Schepers¹,

Asselman²,

Duim³

et al. 2004

Nephron Exp Nephrol

View full text Add to dashboard Cite

Background/Aim: Retention of crystals in the kidney ultimately leads to renal stone formation. Hyaluronan (HA) has been identified as binding molecule for calcium oxalate monohydrate crystals. The association of high molecular mass (M_r) HA with cell surface receptors such as CD44 gives rise to pericellular matrix (PCM) formation by many eukaryotic cells in culture. Here, we study the ability of several renal tubular cell lines to assemble PCMs and to synthesize high-M_r HA during proliferation in relation to crystal retention. Methods: PCM assembly by MDCK-I, MDCK-II, and LLC-PK₁ cells was visualized by particle exclusion assay. Metabolic labeling studies were performed to estimate the cellular production of HA. The expression of CD44 and HA was studied using fluorescent probes, and crystal binding was quantified with radiolabeled calcium oxalate monohydrate. Results: PCMs were formed, and HA was expressed by most MDCK-I and some MDCK-II, but not by LLC-PK₁ cells. All cell types expressed CD44 at their apical surface. MDCK-I and MDCK-II cells secreted, respectively, 14.7 ± 1.6 and 0.5 ± 0.2 pmol [³H]glucosamine incorporated in high-M_r HA, whereas LLC-PK₁ cells did not secrete HA. Streptomyces hyaluronidase treatment significantly decreased crystal binding (µg/cm²) to MDCK-I cells (from 8.6 ± 0.4 to 3.9 ± 0.9), but hardly to MDCK-II cells (from 10.2 ± 0.2 to 9.6 ± 0.1) or LLC-PK₁ cells (from 10.2 ± 0.8 to 9.9 ± 0.3). Conclusions: There are various forms of crystal binding to renal tubular cells in culture. Crystal attachment to MDCK-I and some MDCK-II cells involves PCM assembly that requires high-M_r HA synthesis. HA production and PCM formation do not play a role in crystal binding to LLC-PK₁ and the majority of MDCK-II cells. It remains to be determined which form of binding is involved in renal stone disease.

show abstract

“…Crystal binding is significantly reduced by enzymatic removal of HA. Pretreatment of MDCK cells with polyclonal antibodies against OPN as well as transfection of NRK52E cells with antisense OPN cDNA also reduces adhesion of CaOx crystals [8]. …”

Section: Alteration Of Membrane Structure and Crystal Retentionmentioning

confidence: 99%

Role of Renal Epithelial Cells in the Initiation of Calcium Oxalate Stones

Khan¹

2004

Nephron Exp Nephrol

112

View full text Add to dashboard Cite

Normal urinary environment is inhibitory to crystallization. Occasional crystals are internalized by the renal epithelial cells and sequestered to lysosomes or externalized into the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal cells to increase the synthesis of osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E₂, which are known mediators of the inflammatory processes and extracellular matrix production. Osteopontin and bikunin are also modulators of crystallization. Exposed renal epithelial cells are often injured and go through apoptosis and/or necrosis initiating a cascade of events leading to further crystallization, crystal retention and development of stone nidi. Reactive oxygen species are produced during the interactions between the oxalate/crystals and renal cells and are responsible for the various cellular responses. Calcium oxalate crystal deposition in the rat kidneys also activates the renin-angiotensin system. Both oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated protein kinase in the exposed tubular cells. Extracellular environment changes from one that inhibits crystal nucleation, growth, aggregation and retention to that, which promotes these processes.

show abstract

Interaction between Osteopontin on Madin Darby Canine Kidney Cell Membrane and Calcium Oxalate Crystal

Cited by 41 publications

References 26 publications

Effect of Angiotensin II Receptor Blockage on Osteopontin Expression and Calcium Oxalate Crystal Deposition in Rat Kidneys

Effect of Angiotensin II Receptor Blockage on Osteopontin Expression and Calcium Oxalate Crystal Deposition in Rat Kidneys

Pericellular Matrix Formation by Renal Tubule Epithelial Cells in Relation to Crystal Binding

Role of Renal Epithelial Cells in the Initiation of Calcium Oxalate Stones

Contact Info

Product

Resources

About