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.

Nyckelord

Animals

Extracellular Matrix Proteins

genetics

GTP-Binding Proteins

genetics

Gene Expression Profiling

Gene Expression Regulation

Growth Hormone

secretion

Insulin-Like Growth Factor I

genetics

physiology

Insulin-Like Growth Factor II

analysis

genetics

metabolism

Kidney

anatomy & histology

metabolism

Liver

metabolism

Mice

Mice

Knockout

Oligonucleotide Array Sequence Analysis

Organ Size

Potassium

metabolism

urine

Protein-Lysine 6-Oxidase

genetics

RNA

Messenger

analysis

Reverse Transcriptase Polymerase Chain Reaction

Sodium

metabolism

urine

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