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- Title
Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure.
- Authors
Santos, Soledad; Bosch, Ricardo J.; Ortega, Arantxa; Largo, Raquel; Fernández-Agulló, Teresa; Gazapo, Rosa; Egido, Jesús; Esbrit, Pedro
- Abstract
Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure. Background. Parathyroid hormone (PTH)-related protein (PTHrP) is present in many normal tissues, including the kidney. Current evidence supports that PTHrP is involved in renal pathophysiology, although its role on the mechanisms of renal damage and/or repair is unclear. Our present study examined the changes in PTHrP and the PTH/PTHrP receptor (type 1) in folic acid-induced acute renal failure in rats. The possible role of PTHrP on the process of renal regeneration following folic acid administration, and potential interaction between angiotensin II (Ang II) and endothelin-1, and PTHrP, were examined in this animal model. Methods. PTHrP, PTH/PTHrP receptor, ACE, and preproendothelin-1 (preproET-1) mRNA levels in the rat kidney were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and/or RNase protection assay. Immunohistochemistry also was performed for PTHrP, the PTH/PTHrP receptor, and Ang II in the renal tissue of folic acid-injected rats. The role of PTHrP on tubular cell proliferation following folic acid injury was investigated in vitro in rat renal epithelial cells (NRK 52E). PTHrP secretion in the medium conditioned by these cells was measured by an immunoradiometric assay specific for the 1-36 sequence. Results. Using RT-PCR, PTHrP mRNA was rapidly (1 hour) and maximally increased (3-fold) in the rat kidney after folic acid, decreasing after six hours. At 72 hours, renal function was maximally decreased in these rats, associated with an increased PTHrP immunostaining in both renal tubules and glomeruli. In contrast, the PTH/PTHrP receptor mRNA (RNase protection assay) decreased shortly after folic acid administration. Moreover, PTH/PTHrP receptor immunostaining dramatically decreased in renal tubular cell membranes after folic acid. A single subcutaneous administration of PTHrP (1-36), 3 or 50 μg/kg body weight, shortly after folic...
- Subjects
PARATHYROID hormone-related protein; ACUTE kidney failure; LABORATORY rats
- Publication
Kidney International, 2001, Vol 60, Issue 3, p982
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.060003982.x