Rapamycin induces growth retardation by disrupting angiogenesis in the growth plate
| Autor: | Flor A. Ordoñez, Eduardo Carbajo-Pérez, Julián Rodríguez-Suárez, Oscar Alvarez-Garcia, Fernando Santos, Enrique García-López, Helena Gil-Peña, Vanessa Loredo |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Angiogenesis medicine.medical_treatment Neovascularization Physiologic Osteoclasts Growth Receptor IGF Type 1 chemistry.chemical_compound Chondrocytes children Osteoclast Internal medicine medicine Animals Growth factor receptor inhibitor pediatric kidney transplantation Growth Plate RNA Messenger Insulin-Like Growth Factor I Antibacterial agent Sirolimus vascular endothelial growth factor business.industry Growth factor Rats Endothelial stem cell Vascular endothelial growth factor Transplantation medicine.anatomical_structure Endocrinology chemistry Animals Newborn Nephrology business Immunosuppressive Agents transplantation |
| Zdroj: | Kidney international. 78(6) |
| ISSN: | 1523-1755 |
| Popis: | Rapamycin, a potent immunosuppressant used in renal transplantation, has been reported to impair longitudinal growth in experimental studies. Rapamycin is both antiproliferative and antiangiogenic; therefore, it has the potential to disrupt vascular endothelial growth factor (VEGF) action in the growth plate and to interfere with insulin-like growth factor I (IGF-I) signaling. To further investigate the mechanisms of rapamycin action on longitudinal growth, we gave the 4-week-old rats rapamycin daily for two weeks. Compared with a vehicle-treated group, rapamycin-treated animals were severely growth retarded and had marked alterations in the growth plate. Vascular invasion was disturbed in the rapamycin group, there was a significant reduction in osteoclast cells near the chondro-osseus junction, and there was lower VEGF protein and mRNA expression in the terminal chondrocytes of the growth cartilage. Compared with the control group, the rapamycin group had higher levels of circulating IGF-I as well as the mRNAs for IGF-I and of the receptors of IGF-I and growth hormone in the liver but not in the growth cartilage. Thus our findings explain the adverse effect of rapamycin on growth plate dynamics. This should be taken into account when the drug is administered to children. |
| Databáze: | OpenAIRE |
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