Immunohistochemical localization and mRNA quantification of osteopontin and Tamm-Horsfall protein in canine renal tissue after potassium oxalate injection

Abstract

BackgroundUrinary macromolecules contribute to promoting or inhibiting crystal retention in renal tissue and stone formation. Osteopontin (OPN) and Tamm-Horsfall protein (THP) are the most important proteins involved in this process. Although these two proteins were discovered a long time ago, their role in setting kidney stone formation has not yet been fully investigated. We conducted a study to explore the role of OPN and THP in canine renal oxalosis. Ten dogs were carefully examined prior to the study. Six dogs were assigned to the treatment group and were injected intravenously with 0.5 M potassium oxalate (KOx). The other four dogs were assigned to a control group and were injected intravenously with 0.9% NaCl three times a day (tid) for 7 consecutive days. Then kidneys were harvested for pathological, immunohistochemical examination and OPN and THP mRNA expression levels were quantified by quantitative real-time PCR.ResultsCalcium oxalate crystals deposition was observed in both renal cortex and medulla. Immunohistochemistry examination revealed increased tissue expression of OPN in the renal tissue while THP was significantly decreased. OPN mRNA expression level significantly increased in treated dogs compared to that in the controls, while THP mRNA level significantly decreased.ConclusionTogether, these results suggest that THP and OPN are both involved in the pathogenesis and response to oxalate exposure.

The effects of Urtica dioica L. ethanolic extract against urinary calculi in rats

“…In previous studies, an increase in KIM-1 immunoreactivity has been reported semi-quantitatively in the rat kidney tissue after a 1-week exposure to 1% EG [29]. Similar to these studies, EG group showed intense KIM-1 immunostaining compared to the control group but showed a significant reduction in the treatment and pretreatment groups of UD in our study [38]. Many studies have shown that OPN expression is regulated as a protective response to crystal formation and high phosphate levels [39,40,41].…”

Cisplatin nephrotoxicity in male beagle dogs: next-generation protein kidney safety biomarker tissue expression and related changes in urine

“…34 The up-regulated corticomedullary OPN mRNA expression level changes in macrodissected cortices and medulla and localization of enhanced OPN immunohistochemistry staining revealed the pathogenesis of chemically-induced mineralization (oxalosis) in naïve adult dog kidneys following exposures to potassium oxalate solutions. Endogenous OPN protein in kidneys is responsible for binding to calcium salts to prevent the formation of calcium oxalate crystals.…”

Renal biomarkers in domestic species

“…The biologic function of the protein is still not fully understood, but it is believed to have roles in water and electrolyte balance in the thick ascending limb of Henle's loop, defense against UTI, prevention against the formation of kidney stones, and in innate immunity of the kidney . Normal urine has high concentrations of THP, and significantly reduced urinary THP concentrations and uTHP/c are seen in dogs and cats with renal disease, including CKD . Furthermore, uTHP/c correlates negatively with plasma creatinine concentration and UPC .…”