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

Kidney Int. 1999 Jan;55(1):82-90. doi: 10.1046/j.1523-1755.1999.00241.x.


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 gene expression was observed in the renal cortex of BSA-overloaded rats compared with UNX-control rats.

Conclusions: These results indicate that PTHrP can be added to the group of genes that are up-regulated in proximal tubular cells in response to intense proteinuria. Our results, together with previous findings, suggest that the vasoactive hormones angiotensin II and endothelin-1 could participate in the PTHrP production in the renal cortex of BSA-overloaded rats. Further experiments are required to clarify the mechanisms of PTHrP up-regulation and its possible role in the response to renal damage in this animal model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cattle
  • DNA Primers / genetics
  • Disease Models, Animal
  • Endothelin-1
  • Endothelins / genetics
  • Female
  • Gene Expression
  • Immunohistochemistry
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Nephrectomy
  • Parathyroid Hormone-Related Protein
  • Peptidyl-Dipeptidase A / genetics
  • Protein Precursors / genetics
  • Proteins / genetics*
  • Proteins / metabolism*
  • Proteinuria / etiology
  • Proteinuria / genetics
  • Proteinuria / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone / genetics*
  • Receptors, Parathyroid Hormone / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Albumin, Bovine / administration & dosage


  • DNA Primers
  • Endothelin-1
  • Endothelins
  • Parathyroid Hormone-Related Protein
  • Protein Precursors
  • Proteins
  • RNA, Messenger
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone
  • Serum Albumin, Bovine
  • Peptidyl-Dipeptidase A