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Proliferative glomerulonephritis is characterized by local inflammation and mesangial cell deterioration, followed by mesangial proliferation and glomerular healing. Parathyroid-hormone-related peptide (PTHrP) is a mesangial cytokine-like growth factor implicated in mesangial proliferation and survival. No data are available about its role in glomerulonephritis. Herein, we analyzed the expression and role of PTHrP in glomerular inflammation and healing in an experimental model of glomerulonephritis induced by intravenous injection of Habu-snake venom in mice. The temporal analysis showed marked renal damage in the first days after venom injection and beginning of recovery within seven days. Glomerular expression of PTHrP (transcript and protein) was observed in the very early phase after venom injection (day-1 to day-3), along with an inflammatory environment. The inactivation of secreted PTHrP with PTHrP-neutralizing antibody (PTH2E11, 120 μg i.p. daily) reduced the markers of local inflammation (expression of MCP-1, RANTES, Cox-2, IL-6, and macrophage infiltration) and abolished the expression of PTHrP itself. Moreover, the glomerular cell proliferation was hampered, and the healing process was prevented on day-7 post-venom injection. These results show that PTHrP has antinomic actions in glomerulonephritis, participating to both the pro-inflammatory condition and the healing process. Our work reveals the essential role of PTHrP in the early glomerular repair in an experimental model of glomerulonephritis.
This article was published in the following journal.
Name: The American journal of pathology
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A parathyroid hormone receptor subtype that recognizes both PARATHYROID HORMONE and PARATHYROID HORMONE-RELATED PROTEIN. It is a G-protein-coupled receptor that is expressed at high levels in BONE and in KIDNEY.
A ubiquitously expressed, secreted protein with bone resorption and renal calcium reabsorption activities that are similar to PARATHYROID HORMONE. It does not circulate in appreciable amounts in normal subjects, but rather exerts its biological actions locally. Overexpression of parathyroid hormone-related protein by tumor cells results in humoral calcemia of malignancy.
Cell surface proteins that bind PARATHYROID HORMONE with high affinity and trigger intracellular changes which influence the behavior of cells. Parathyroid hormone receptors on BONE; KIDNEY; and gastrointestinal cells mediate the hormone's role in calcium and phosphate homeostasis.
A parathyroid hormone receptor subtype found in the BRAIN and the PANCREAS. It is a G-protein-coupled receptor with a ligand specificity that varies between homologs from different species.
Pathological processes of the PARATHYROID GLANDS. They usually manifest as hypersecretion or hyposecretion of PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.
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Complementary and Alternative Medicine
Alternative medicine are whole medical systems that did not fit with conventional medicine as they have completely different philosophies and ideas on the causes of disease, methods of diagnosis and approaches to treatment. Although often overlapping, co...