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Levels of circulating plasma hepatocyte growth factor are increased in interleukin-6-deficient mice after partial hepatectomy
Poster abstracts 203
Miscellaneous Experimental studies Plasma concentrations of free insulin-like growth factor I are normal in children with simple obesity T. Hasegawa ~, S. Kusano 2, Y. Hasegawa ~, M. Takada 3 Wokyo Metropolitan Kiyose Children's Hospital, Tokyo, 2Kusano Paediatric Clinic, Tochigi and 3Yuka Medias, Ibaraki, Japan
Plasma concentrations of insulin-like growth factor binding protein-1 (IGFBP-1)are decreased in children with simple obesity, which may result in elevated levels of free insulin-like growth factor I (IGF-I).The purpose of this study was to determine the plasma concentration of free IGF-I and the mechanism by which free IGF-I is regulated in children with simple obesity. Twenty-three children with simple obesity (16 boys, 7 girls; age, 3.2-15.5 years; obesity score, 22.0-92.5%) were investigated. Plasma free IGF-I and plasma total IGF-I were measured using immunoradiometric assays. IGFBP-1 and IGFBP-3 were measured by radioimmunoassay, and IGFBP-3 proteolytic activity was determined by an IGFBP-3 protease assay. Plasma free 1GF-Iwas
within the age-matched 5th-95th percentile in 21 children. Serum IGFBP-1 was lower than the age-matched mean by at least 2 SEM in all children, and in 15 children it was below the limit of detection of the assay (0.3 ng/1). Serum IGFBP-3 was within _+2 SD of the age-matched mean in 18 of the children. None of the children showed significant IGFBP-3 proteolytic activity. It is concluded that the plasma concentration of free IGF-I was normal in children with simple obesity, even though IGFBP-1 levels were low. As more than 90% of circulating IGFBP is IGFBP-3, normal levels of IGFBP-3 and no evidence of IGFBP-3 proteolytic activity could explain the normal levels of plasma free IGF-I in children with simple obesity.
Levels of circulating plasma h e p a t o c y t e growth factor are increased in interleukin.6-deficient mice after partial h e p a t e c t o m y V. R. Wallenius, S. Skrtic and J.-O. Jansson Department of Internal Medicine, Research Center for Endocrinology and Metabolism (RCEM), Sahlgrenska University Hospital, GSteborg, Sweden
Interleukin-6-deficient mice display severely impaired liver regeneration after partial hepatectomy. 1 Hepatocyte growth factor (HGF) is the most potent known hepatocyte mitogen in vitro. In most studies of partial hepatectomy, rodents display an increase in the expression of HGF mRNA in the liver, but no change in circulating plasma HGF levels. However, in rat models of hepatocyte damage, such as fulminant hepatitis, the circulating HGF levels are increased. Given the impaired liver regeneration and the enhanced rate of necrosis after hepatectomy in mice with a targeted disruption of the IL-6 gene (IL-6 -/-; generously provided by Dr Manfred Kopf), we examined the circulating levels of HGF in these mice. IL-6 - / and normal mice were subjected to 2/3 partial hepatectomy. The livers and plasma were collected at different time points after surgery. DNA synthesis was measured by the rate of incorporation of [BH]thymidine into DNA. For the measurement of circulating immunoreactive HGF, an HGF ELISA (R&D Systems, Abingdon, UK) was used. The IL-6 - / - mice had a severe
dejay in the initiation of DNA synthesis and imp p~ralred recovery of-liver weight after partial hepatectomy. The circulating levels of immunoreactive HGF after partial hepatectomy were higher in plasma of IL-6 - / - mice than in normal mice at 10, 18 and 36 hours (P < 0.05). The HGF levels in IL-6 - / - mice peaked at 36 hours with a fourfold increase compared with basal levels. In the present study, the normal mice displayed no significant increase in plasma HGF after hepatectomy. This study confirms the results obtained using another strain of 1L-6-deficient mice, that is, IL-6 is important for liver regeneration, j The levels of circulating HGF were increased in the IL-6-deficient mice, but not in normal mice. It is unknown if this is related to the previously reported necrosis in the regenerating liver of the IL-6 - / - mice. Cressman DE, Greenbaum LE, DeAngelisRA, Ciliberto G, Furth EE, Poli V, Taub R. Liver failure and defective hepatocyte regeneration in interleukin-6-deficientmice. Science 1996; 274: 1379-1383.
Miscellaneous Experimental studies Plasma concentrations of free insulin-like growth factor I are normal in children with simple obesity T. Hasegawa ~, S. Kusano 2, Y. Hasegawa ~, M. Takada 3 Wokyo Metropolitan Kiyose Children's Hospital, Tokyo, 2Kusano Paediatric Clinic, Tochigi and 3Yuka Medias, Ibaraki, Japan
Plasma concentrations of insulin-like growth factor binding protein-1 (IGFBP-1)are decreased in children with simple obesity, which may result in elevated levels of free insulin-like growth factor I (IGF-I).The purpose of this study was to determine the plasma concentration of free IGF-I and the mechanism by which free IGF-I is regulated in children with simple obesity. Twenty-three children with simple obesity (16 boys, 7 girls; age, 3.2-15.5 years; obesity score, 22.0-92.5%) were investigated. Plasma free IGF-I and plasma total IGF-I were measured using immunoradiometric assays. IGFBP-1 and IGFBP-3 were measured by radioimmunoassay, and IGFBP-3 proteolytic activity was determined by an IGFBP-3 protease assay. Plasma free 1GF-Iwas
within the age-matched 5th-95th percentile in 21 children. Serum IGFBP-1 was lower than the age-matched mean by at least 2 SEM in all children, and in 15 children it was below the limit of detection of the assay (0.3 ng/1). Serum IGFBP-3 was within _+2 SD of the age-matched mean in 18 of the children. None of the children showed significant IGFBP-3 proteolytic activity. It is concluded that the plasma concentration of free IGF-I was normal in children with simple obesity, even though IGFBP-1 levels were low. As more than 90% of circulating IGFBP is IGFBP-3, normal levels of IGFBP-3 and no evidence of IGFBP-3 proteolytic activity could explain the normal levels of plasma free IGF-I in children with simple obesity.
Levels of circulating plasma h e p a t o c y t e growth factor are increased in interleukin.6-deficient mice after partial h e p a t e c t o m y V. R. Wallenius, S. Skrtic and J.-O. Jansson Department of Internal Medicine, Research Center for Endocrinology and Metabolism (RCEM), Sahlgrenska University Hospital, GSteborg, Sweden
Interleukin-6-deficient mice display severely impaired liver regeneration after partial hepatectomy. 1 Hepatocyte growth factor (HGF) is the most potent known hepatocyte mitogen in vitro. In most studies of partial hepatectomy, rodents display an increase in the expression of HGF mRNA in the liver, but no change in circulating plasma HGF levels. However, in rat models of hepatocyte damage, such as fulminant hepatitis, the circulating HGF levels are increased. Given the impaired liver regeneration and the enhanced rate of necrosis after hepatectomy in mice with a targeted disruption of the IL-6 gene (IL-6 -/-; generously provided by Dr Manfred Kopf), we examined the circulating levels of HGF in these mice. IL-6 - / and normal mice were subjected to 2/3 partial hepatectomy. The livers and plasma were collected at different time points after surgery. DNA synthesis was measured by the rate of incorporation of [BH]thymidine into DNA. For the measurement of circulating immunoreactive HGF, an HGF ELISA (R&D Systems, Abingdon, UK) was used. The IL-6 - / - mice had a severe
dejay in the initiation of DNA synthesis and imp p~ralred recovery of-liver weight after partial hepatectomy. The circulating levels of immunoreactive HGF after partial hepatectomy were higher in plasma of IL-6 - / - mice than in normal mice at 10, 18 and 36 hours (P < 0.05). The HGF levels in IL-6 - / - mice peaked at 36 hours with a fourfold increase compared with basal levels. In the present study, the normal mice displayed no significant increase in plasma HGF after hepatectomy. This study confirms the results obtained using another strain of 1L-6-deficient mice, that is, IL-6 is important for liver regeneration, j The levels of circulating HGF were increased in the IL-6-deficient mice, but not in normal mice. It is unknown if this is related to the previously reported necrosis in the regenerating liver of the IL-6 - / - mice. Cressman DE, Greenbaum LE, DeAngelisRA, Ciliberto G, Furth EE, Poli V, Taub R. Liver failure and defective hepatocyte regeneration in interleukin-6-deficientmice. Science 1996; 274: 1379-1383.