Renal expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in a rat model of tubulointerstitial damage.

Renal expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in a rat model of tubulointerstitial damage. Background. PTHrP, which appears to act as a growth/differentiation factor in a variety of tissues, is present in the kidney; however, its role is unclear. Methods. The expression of PTHrP and the PTH/PTHrP receptor were investigated by reverse transcription-polymerase chain reaction (RT–PCR) and immunohistochemistry in the remnant kidney of uninephrectomized (UNX) rats after protein overloading [1 g/day of bovine serum albumin (BSA)]. Results. Compared with UNX-control rats, proteinuria in BSA-overloaded animals was detected within the first 24 hours and increased during the entire study period (28 days). Kidney examination by light microscopy showed no significant renal lesions at day 1 of BSA treatment, whereas at days 8 and 28, tubular lesions, infiltration of mononuclear cells, and mesangial expansion were observed. PTHrP mRNA expression in the renal cortex was already increased at day 1 (fourfold) and plateaued between days 8 and 28 (12- and 15-fold, respectively) in BSA-overloaded animals compared with UNX-control rats. At day 8, immunohistochemical analysis with two different anti-PTHrP antibodies showed a dramatic increase of PTHrP staining in the damaged proximal and distal tubules from BSA-overloaded rats with respect to UNX-control rats. Moreover, intense PTHrP immunostaining was also observed in glomerular mesangial and endothelial cells in BSA-overloaded rats, but not in the UNX-control rats. A reciprocal decrease of PTH/PTHrP receptor mRNA and immunostaining, without significant changes in the cellular localization (proximal and distal tubule, and glomerular mesangial and epithelial cells) of the PTH/PTHrP receptor positivity was found to occur in the renal cortex of BSA-overloaded rats. At day 8, coinciding with the up-regulation of PTHrP, an increase in the angiotensin converting enzyme and preproendothelin-1... [ABSTRACT FROM AUTHOR]