Svensson Johan, Tivesten Asa, Sjögren Klara, Isaksson Olle, Bergström Göran, Mohan Subburaman, Mölne Johan, Isgaard Jörgen, Ohlsson Claes
Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden.
J Endocrinol. 2007 Jun;193(3):359-66. doi: 10.1677/JOE-07-0024.
The GH/-IGF-I axis is important for kidney size and function and may also be involved in the development of renal failure. In this study, the role of liver-derived endocrine IGF-I for kidney size and function was investigated in mice with adult liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice). These mice have an 80-85% reduction of serum IGF-I level and compensatory increased GH secretion. Seven-month-old as well as 24-month-old LI-IGF-I(-/-) mice had decreased kidney weight. Glomerular filtration rate, assessed using creatinine clearance as well as creatinine clearance corrected for body weight, was unchanged. The 24-h urine excretion of sodium and potassium was increased in the LI-IGF-I(-/-) mice. In the 24-month-old mice, there was no between-group difference in kidney morphology. Microarray and real-time PCR (RT-PCR) analyses showed a high renal expression of IGF-II in the control mice, whereas in the LI-IGF-I(-/-) mice, there was a tissue-specific decrease in the renal IGF-II mRNA levels (-79%, P < 0.001 vs controls using RT-PCR). In conclusion, deficiency of circulating liver-derived IGF-I in mice results, despite an increase in GH secretion, in a global symmetrical decrease in kidney size, increased urinary sodium and potassium excretion, and a clear down regulation of renal IGF-II expression. However, the LI-IGF-I(-/-) mice did not develop kidney failure or nephrosclerosis. One may speculate that liver-derived endocrine IGF-I induces renal IGF-II expression, resulting in symmetrical renal growth.
生长激素/胰岛素样生长因子-I（GH/-IGF-I）轴对肾脏大小和功能很重要，也可能参与肾衰竭的发展。在本研究中，我们在成年肝脏特异性IGF-I失活的小鼠（LI-IGF-I(-/-)小鼠）中研究了肝脏来源的内分泌IGF-I对肾脏大小和功能的作用。这些小鼠的血清IGF-I水平降低了80 - 85%，同时伴有代偿性GH分泌增加。7月龄和24月龄的LI-IGF-I(-/-)小鼠肾脏重量均降低。使用肌酐清除率以及校正体重后的肌酐清除率评估的肾小球滤过率未发生变化。LI-IGF-I(-/-)小鼠的24小时尿钠和钾排泄量增加。在24月龄小鼠中，两组间肾脏形态无差异。基因芯片和实时定量聚合酶链反应（RT-PCR）分析显示，对照小鼠肾脏中IGF-II表达较高，而在LI-IGF-I(-/-)小鼠中，肾脏IGF-II mRNA水平出现组织特异性降低（-79%，与对照组相比，RT-PCR结果P < 0.001）。总之，尽管GH分泌增加，但小鼠体内循环肝脏来源的IGF-I缺乏导致肾脏大小整体对称性减小、尿钠和钾排泄增加以及肾脏IGF-II表达明显下调。然而，LI-IGF-I(-/-)小鼠并未发生肾衰竭或肾硬化。人们可以推测，肝脏来源的内分泌IGF-I诱导肾脏IGF-II表达，从而导致肾脏对称性生长。
