Gil Helena, Lozano Juan J, Alvarez-García Oscar, Secades-Vázquez Pablo, Rodríguez-Suárez Julián, García-López Enrique, Carbajo-Pérez Eduardo, Santos Fernando
Hospital Universitario Central de Asturias, Spain.
Growth Horm IGF Res. 2008 Aug;18(4):353-9. doi: 10.1016/j.ghir.2008.01.009. Epub 2008 Mar 10.
Treatment with growth hormone (GH) improves growth retardation of chronic renal failure. cDNA microarrays were used to investigate GH-induced modifications in gene expression in the tibial growth plate of young rats.
RNA was extracted from the tibial growth plate from two groups, untreated and treated with GH, of young rats made uremic by subtotal nephrectomy (n=10). To validate changes shown by the Agilent oligo microarrays, some modulated genes known to play a physiological role in growth plate metabolism were analyzed by real-time quantitative polymerase chain reaction (qPCR).
The microarrays showed that GH modified the expression of 224 genes, 195 being upregulated and 29 downregulated. qPCR results confirmed the sense of expression change found in the arrays for insulin-like growth factor I, insulin-like growth factor II, collagen V alpha 1, bone morphogenetic protein 3 and proteoglycan type II.
This study shows for the first time the profile of growth plate gene expression modifications caused by GH treatment in experimental uremia and provides a basis to further investigate selected individual genes with potential implication in the stimulating effect on the growth of GH treatment in chronic renal failure.
生长激素(GH)治疗可改善慢性肾衰竭患者的生长迟缓。利用cDNA微阵列研究GH对幼鼠胫骨生长板基因表达的影响。
从两组通过肾大部切除术诱导为尿毒症的幼鼠(n = 10)的胫骨生长板中提取RNA,一组未接受治疗,另一组接受GH治疗。为验证安捷伦寡核苷酸微阵列显示的变化,通过实时定量聚合酶链反应(qPCR)分析了一些已知在生长板代谢中起生理作用的调控基因。
微阵列显示GH改变了224个基因的表达,其中195个上调,29个下调。qPCR结果证实了阵列中发现的胰岛素样生长因子I、胰岛素样生长因子II、胶原蛋白Vα1、骨形态发生蛋白3和蛋白聚糖II型的表达变化趋势。
本研究首次展示了实验性尿毒症中GH治疗引起的生长板基因表达变化情况,并为进一步研究特定的单个基因提供了基础,这些基因可能对GH治疗慢性肾衰竭的生长刺激作用具有潜在影响。