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Abstract: Objective: Intrauterine growth restriction (IUGR) is associated with hypertension and chronic kidney disease in adulthood. Postnatal overnutrition after IUGR may be of pathogenic importance for the development of diabetes and cardiovascular disease. This study was to identify the effects of IUGR and a postnatal high-protein diet on the kidneys in adult rats. Methods: Intrauterine growth restriction was induced in Sprague-Dawley rats by isocaloric protein restriction in pregnant dams. IUGR pups were divided into two groups that were a standard-protein diet (IUGR group) or a high-protein diet (HP group). A comparative proteomic method was used to study the differences of protein expression profiles between normal adult rats and adult rats with IUGR and the effects of a postnatal high-protein diet on the protein expression profiles of the kidneys. Results: The IUGR adults had higher urinary excretion of protein and blood pressure than controls and the HP diet caused more severe hypertension and proteinuria than IUGR itself. The differential proteomic expression analysis found 12 proteins that had significantly differential expression between the IUGR and control groups, which were transcription regulators and structural molecules. The differential proteomic expression analysis between the HP and control groups found 13 proteins that had significantly differential expression and were involved primarily in body metabolism, oxidation reduction, and apoptosis regulation. Conclusion: An HP diet intervention after IUGR worsens the severity of hypertension and proteinuria, and this study may provide valuable experimental evidence of proteins involved in the pathogenesis of kidney disease in IUGR and the effect of postnatal overnutrition. [Copyright &y& Elsevier]

Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment. The aim of this study was to test the hypothesis that IUGR affects expression of key proteins that regulate nephrogenesis, by a comparative proteomic approach. IUGR was induced in Sprague–Dawley (SD) rats by isocaloric protein restriction in pregnant dams. A series of methods, including two-dimensional gel electrophoresis (2-DE), silver staining, mass spectrometry and database searching was used. After silver staining, 2-DE image analysis detected an average 730 ± 58 spots in the IUGR group and 711 ± 73 spots in the control group. The average matched rate was 86% and 81%, respectively. The differential proteomic expression analysis found that 11 protein spots were expressed only in the IUGR group and one in the control group. Seven protein spots were up-regulated more than fivefold and two were down-regulated more than fivefold in the IUGR group compared with those in control group. These 21 protein spots were preliminarily identified and were structural molecules, including vimentin, perlecan, gamma-actin and cytokeratin 10, transcription regulators, transporter proteins, enzymes, and so on. These proteins were involved primarily in energy metabolism, oxidation and reduction, signal transduction, cell proliferation and apoptosis. Data from this study may provide, at least partly, evidence that abnormality of metabolism, imbalance of redox and apoptosis, and disorder of cellular signal and cell proliferation may be the major mechanisms responsible for abnormal nephrogenesis in IUGR. [ABSTRACT FROM AUTHOR]