Here, we quantitatively investigate the role of phosphorylation in interactions with calcium oxalate monohydrate crystals (COM), using synthetic peptides corresponding to the sequence 220-235 in osteopontin, a major inhibitor of kidney stone-related COM formation.
The aim of the study was assessment of four selected macromolecules level: osteopontin, calgranulin, uromodulin and bikunin in fresh morning urine sample in children with nephrolithiasis in the course of idiopathic hypercalciuria.
The purpose of this study is to evaluate the correlation between urinary OPN level and kidney stone formation and effect of nutrition on OPN level in nephrolithiasis.
Here, we investigated the effects of different phosphorylated states of a synthesized peptide of OPN (the ASARM peptide; acidic, serine- and aspartate-rich motif) on calcium oxalate dihydrate (COD) crystals, a major mineral phase of kidney stones.
The results advocate possible association of osteopontin with ER stress, thus suggesting that the ER could be a new target for developing therapeutic regimes for kidney stones.
RT-PCR analysis and immunocytochemistry of NRK-52E cells revealed the up-regulation of inflammatory and stress biomarkers OPN and HSP-70, respectively, in response to COM toxicity; which diminished significantly in the presence of kidney stone matrix proteins.
To further investigate the role of Opn, we used a double-knockout strategy, which provides evidence that loss of Opn worsens the nephrocalcinosis and nephrolithiasis observed in these mice on a high-phosphate diet.
We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses.
Taken together, our findings suggest that gallotannin can contribute to nephrolithiasis prevention via direct effects on renal epithelial cells including suppression of COM binding and MCP-1 and OPN expression, along with augmenting antioxidant activity.
SPP1 polymorphisms were found to be associated with nephrolithiasis and it may be suggested that SPP1 gene polymorphism could be a useful marker for evaluation of the early genetic risk factor in childhood nephrolithiasis.
These results are the first to demonstrate the existence of T-593A promoter polymorphism of the OPN gene and significant association with risk of developing nephrolithiasis.
Based on these data, it is proposed that during urolithiasis, secretion of osteopontin (uropontin) and osteocalcin (or osteocalcin-related gene/protein), and the subsequent incorporation of these proteins into kidney stone matrix, may influence the nucleation, growth processes, aggregation, and/or tubular adhesion of renal calculi in mammalian kidneys.