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Expression of Tamm-Horsfall protein in stone-forming rat models
O Miyake1, T Yoshioka, K Yoshimura
1Department of Urology, Osaka University Medical School, Japan.
Objectives:
To examine the expression of Tamm-Horsfall protein (THP) and calcium oxalate deposition in three rat models to clarify whether THP plays an active role in crystal formation or whether crystals induce the secretion of this protein.
Materials And Methods:
A stone-forming rat model (model 1) with marked tubular dilatation in an entire kidney was produced by rendering Wistar rats (aged 8 weeks) hyperoxaluric and hypercalciuric, through compulsorily feeding with 0.12 mL of 5% ethylene glycol (in two doses daily) and 0.5 microgram of vitamin D3 every other day. Two other rat models were also produced. Model 2 comprised stone-forming rats with minimal tubular dilatation, achieved by giving rats the same dose of ethylene glycol once daily, and model 3 comprised stone-free rats with marked tubular dilatation achieved by unilateral ureteric ligation. The rats' kidneys were resected after 4 weeks and all resected kidneys immunohistochemically stained with an antibody to THP. Simultaneously, the location of calcium oxalate (CaOx) crystals was established with von Kossa staining. The relation between crystals and the secretion of THP was also assessed in vitro. Cultured renal epithelial cells (NRK-52E) were stained with an antibody to THP after they had been cultured for 72 h in a medium containing CaOx crystals.
Results:
In model-1 kidneys with both tubular dilatation and many crystals, there was local and intense expression of THP in many renal tubules. CaOx crystals and the intense expression of THP tended to occur in the same renal tubules. In model 2 kidneys with little tubular dilatation, only a few renal tubules expressed THP strongly and the location of the crystals rarely coincided with that of THP expression. In model 3 kidneys with marked tubular dilatation but no crystals, THP was expressed strongly in many renal tubules. The expression of THP in cultured NRK-52E cells was not stimulated by CaOx crystals.
Conclusions:
The results from the in vivo models suggest that THP did not initiate crystal formation and the strong expression of THP was induced not by crystals but by renal tubular damage caused by tubular dilatation. From the close association of THP and crystals in model 1 kidneys, this protein might play a secondary role as an adhesive, promoting stone formation.