Liver-derived IGF-I regulates kidney size, sodium reabsorption, and renal IGF-II expression.
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.
Svensson
Johan
J
Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden.
Tivesten
Asa
A
Sjögren
Klara
K
Isaksson
Olle
O
Bergström
Göran
G
Mohan
Subburaman
S
Mölne
Johan
J
Isgaard
Jörgen
J
Ohlsson
Claes
C
D000818:Animals; D016326:Extracellular Matrix Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000033:anatomy & histology* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D064547:Myxovirus Resistance Proteins; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D011188:Potassium / Q000378:metabolism / Q000652:urine; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism* / Q000652:urine
D016326:Extracellular Matrix Proteins; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; C077112:Lox protein, mouse; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D012964:Sodium; D008249:Protein-Lysine 6-Oxidase; D019204:GTP-Binding Proteins; D011188:Potassium