EXPRESSION OF TAMM-HORSFALL PROTEIN IN STONE-FORMING RAT MODELS

Objectives To examine the expression of Tamm-Horsfall protein (THP) an d calcium oxalate deposition in three rat models to clarify whether TH P 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 14 weeks) hyperoxaluric a nd hypercalciuric, through compulsorily feeding with 0.12 mL of 5% eth ylene glycol (in two doses daily) and 0.5 mu g of vitamin D3 every oth er day, Two other rat models were also produced, Model 2 comprised sto ne-forming rats with minimal tubular dilatation, achieved by giving ra ts 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 a ll resected kidneys immunohistochemically stained with an antibody to THP. Simultaneously, the location of calcium oxalate (CaOx) crystals w as established with von Kossa staining, The relation between crystals and the secretion of THP nas also assessed in vitro. Cultured renal ep ithelial cells (NRK-52E) were stained with an antibody to THP after th ey had been cultured for 72 h in a medium containing CaOx crystals. Re sults In model-1 kidneys with both tubular dilatation and many crystal s, there was local and intense expression of THP in many renal tubules . CaOx crystals and the intense expression of THP tended to occur in t he same renal tubules. In model 2 kidneys with little tubular dilatati on, only a few renal tubules expressed THP strongly and the location o f the crystals rarely coincided with that of THP expression. In model 3 kidneys with marked tubular dilatation but no crystals, THP was expr essed strongly in many renal tubules, The expression of THP in culture d NRK-52E cells was not stimulated by CaOx crystals, Conclusions The r esults from the in vivo models suggest that THP did not initiate cryst al formation and the strong expression of THP was induced not by cryst als but by renal tubular damage caused by tubular dilatation. From the close association of THP and crystals in model 1 kidneys, this protei n might play a secondary role as an adhesive, promoting stone formatio n.