Hydration status affects osteopontin expression in the rat kidney

Abstract

Osteopontin (OPN) is a secretory protein that plays an important role in urinary stone formation. Hydration status is associated with the development of urolithiasis. This study was conducted to examine the effects of dehydration and hydration on OPN expression in the rat kidney. Animals were divided into three groups, control, dehydrated, and hydrated. Kidney tissues were processed for light and electron microscope immunocytochemistry, in situ hybridization, and immunoblot analysis. Dehydration induced a significant increase in OPN protein expression, whereas increased fluid intake induced a decrease in protein expression. Under control conditions, OPN protein and mRNA expression were only detected in the descending thin limb (DTL). Dehydration induced increased expression in the DTL and the development of detectable expression in the thick ascending limb (TAL). In contrast, OPN expression levels declined to less than the controls in the DTL after hydration, while no expression of either protein or mRNA was detectable in the TAL. Immunoelectron microscopy demonstrated that hydration status altered tubular ultrastructure and intracellular OPN expression in the Golgi apparatus and secretory cytoplasmic vesicles. These data confirm that changes in oral fluid intake can regulate renal tubular epithelial cell OPN expression.

Kidney Stone Prevention

“…From an in vitro stone formation study, it is not unexpected that CaOx crystallization and aggregation decrease after the urine is diluted by hydration in both normal subjects and stone formers [ 31 ]. Expression of a calcium stone modulatory protein, osteopontin (OPN), is also affected by the hydration status [ 32 ]. Note that OPN exhibits dual modulatory roles in kidney stone formation [ 33 ].…”

“…Although it promotes CaOx crystal adhesion on renal tubular cell surfaces [ 34 ] and self-aggregation [ 35 ], it inhibits crystal growth [ 36 ]. OPN expression significantly increases in renal tissue of dehydrated rats, whereas the high fluid intake reduces tissue expression of this protein [ 32 ]. Moreover, renal papillary density, which is elevated in stone formers, significantly declines in patients with increased fluid intake for 12 mo [ 37 ].…”

iTRAQ-Based Comparative Proteomics Analysis of Urolithiasis Rats Induced by Ethylene Glycol

“…Some researchers found OPN to be a powerful synergistic inhibitor of renal calcinosis and stone formation [30,31]. Other studies found that OPN attributed to renal crystal formation in vitro and in vivo [32][33][34][35] by its characteristic structure, including two calcium-binding sites and Arg-Gly-Asp (RGD) sequences. Bhardwaj R found calcium oxalate crystal deposition was associated with the expression of OPN and endoplasmic reticulum stress [36].…”

Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest

“…Interestingly, in the kidney, reduction of OPN decreases the risk of renal stone formation ( Hamamoto et al, 2010 ; Tsuji et al, 2014 ). The hydration state condition can reduce kidney crystal formation by modulating the intrarenal OPN expression ( Lee et al, 2016 ).…”