Mulroney S E, Haramati A, Werner H, Bondy C, Roberts C T, LeRoith D
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, D.C. 20007.
Endocrinology. 1992 Jan;130(1):249-56. doi: 10.1210/endo.130.1.1309331.
There is a developmental difference in the initial phase of compensatory renal growth (CRG) following unilateral nephrectomy (UNX), in that CRG is GH-dependent in adult rats and GH-independent in immature rats. Furthermore, CRG in immature rats is associated with an increase in renal IGF-I mRNA, an effect not seen in adult rats. In this study we have examined the age-related differences in expression of the insulin-like growth factor-I (IGF-I) and IGF-II genes as well as in IGF-I and IGF-II receptors and membrane binding after UNX. Immature (22-24 days of age) and adult (4 months of age) male Wistar rats underwent a sham operation or left UNX and were killed 24 or 48 h later. Levels of mRNA for IGF-I and IGF-II and their receptors were determined in the left (control) and right (compensated) remnant kidneys using solution hybridization/RNase protection assays. Steady state levels of IGF-I mRNA as well as IGF-I receptor and IGF-II/mannose-6-phosphate receptor mRNAs were increased 3- to 4-fold in immature remnant kidneys, but not in adult kidneys. The findings related to IGF-I gene expression were confirmed by in situ hybridization to immature and adult kidney slices. The increase in IGF-I gene expression in the immature remnant kidneys was localized to the thick ascending limbs of the loops of Henle. Furthermore, in concert with the changes in mRNA levels, membrane binding studies showed significant increases in specific binding to IGF-I in cortical membranes and increases in specific binding to IGF-II in whole kidney membranes from immature, but not adult, rats. Thus, these findings demonstrate that the initial phase of CRG in the immature rat is associated with increased renal IGF-I gene expression as well as enhanced specific renal binding of IGF-I and IGF-II to plasma membranes and support the notion that this period of rapid renal growth in the immature UNX rat may involve the paracrine influence of the IGFs.
单侧肾切除（UNX）后代偿性肾生长（CRG）初始阶段存在发育差异，即成年大鼠的CRG依赖生长激素（GH），而未成熟大鼠的CRG不依赖GH。此外，未成熟大鼠的CRG与肾胰岛素样生长因子-I（IGF-I）mRNA增加有关，成年大鼠则未出现这种效应。在本研究中，我们检测了UNX后胰岛素样生长因子-I（IGF-I）和IGF-II基因表达、IGF-I和IGF-II受体以及膜结合方面的年龄相关差异。未成熟（22 - 24日龄）和成年（4月龄）雄性Wistar大鼠接受假手术或左侧UNX，术后24或48小时处死。使用溶液杂交/核糖核酸酶保护分析测定左侧（对照）和右侧（代偿）残余肾中IGF-I和IGF-II及其受体的mRNA水平。未成熟残余肾中IGF-I mRNA以及IGF-I受体和IGF-II/甘露糖-6-磷酸受体mRNA的稳态水平增加了3至4倍，成年肾中则未增加。通过对未成熟和成年肾切片进行原位杂交，证实了与IGF-I基因表达相关的结果。未成熟残余肾中IGF-I基因表达的增加定位于髓袢升支粗段。此外，与mRNA水平变化一致，膜结合研究表明，未成熟大鼠而非成年大鼠的皮质膜中与IGF-I的特异性结合显著增加，全肾膜中与IGF-II的特异性结合增加。因此，这些结果表明，未成熟大鼠CRG的初始阶段与肾IGF-I基因表达增加以及IGF-I和IGF-II与质膜的特异性肾结合增强有关，并支持这样一种观点，即未成熟UNX大鼠快速肾生长的这一时期可能涉及IGF的旁分泌影响。
