Hepatocyte-stimulated expression of hepatocyte growth factor (HGF) in cultured rat hepatic stellate cells

被引:33
|
作者
Skrtic, S
Wallenius, V
Ekberg, S
Brenzel, A
Gressner, AM
Jansson, JO
机构
[1] Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, Div Endocrine, S-41345 Gothenburg, Sweden
[2] Univ Marburg, Dept Clin Chem, D-3550 Marburg, Germany
[3] RWTH Univ Hosp, Cent Lab, Inst Clin Chem & Pathobiochem, Aachen, Germany
关键词
conditioned medium; insulin-like growth factor-1; in vitro; paracrine; rat;
D O I
10.1016/S0168-8278(99)80015-4
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Hepatic stellate cells appear to be the main producers of hepatocyte growth factor of the normal liver. Insulin-like growth factors in doses over 20 ng/ml have been reported to stimulate hepatocyte growth factor production in cultured hepatic stellate cells. The aim of the present study was to investigate whether parenchymal cell conditioned medium had insulin-like growth factor-independent effects on hepatic stellate cells. Methods: Primary rat hepatic stellate cells were cultured for 1-7 days. DNA synthesis was measured by H-3-thymidine incorporation. Hepatocyte growth factor and transforming growth factor beta(1) immunoreactivity was quantified by ELISA. Hepatocyte growth factor mRNA levels were determined with gel RNase protection assay. Parenchymal cell conditioned medium was obtained from hepatocytes cultured for 2 days in medium without added serum or hormones. Results: Incubation of 1-7-day-old hepatic stellate cells for 2 days with parenchymal cell conditioned medium enhanced the medium content of hepatocyte growth factor. Parenchymal cell conditioned medium contained less than 5.0 ng/ml immunoreactive insulin-like growth factor-1 as measured by radio immunoassay. Parenchymal cell conditioned medium did not contain any insulin-like growth factor bioactivity measured as phosphorylation of type 1 insulinlike growth factor receptor beta subunit and a protein with a size consistent with that of insulin receptor substrate-1. The stimulatory effect of parenchymal cell conditioned medium on hepatocyte growth factor was time- and dose-dependent. The effects of a high dose of parenchymal cell conditioned medium (dilution 1:2 containing less than 2.5 ng/ml insulin-like growth factor-1) were additive to that of high doses (100 ng/ml) of insulin-like growth factor-1 or des (1-3) insulin-like growth factor-1, an analogue with low affinity to insulin-like growth factor binding proteins. Neither parenchymal cell conditioned medium nor insulin-like growth factor-1 enhanced transforming growth factor beta(1) immunoreactivity in the medium. Both parenchymal cell conditioned medium and insulin-like growth factor-1 stimulated DNA synthesis in hepatic stellate cells, confirming previous reports. Conclusions: The present results indicate that both insulin-like growth factor-1 and insulin-like growth factor-1-independent factors from hepatocytes can stimulate hepatocyte growth factor production by hepatic stellate cells. Therefore, insulin-like growth factor-1 and other hepatocyte-derived factors may indirectly affect hepatocytes via a paracrine loop.
引用
收藏
页码:115 / 124
页数:10
相关论文
共 50 条
  • [21] HEPATOCYTE GROWTH-FACTOR (HGF) AND CARCINOGENESIS
    MOGHUL, A
    ALARCON, W
    PETERSEN, B
    BELL, A
    DEFRANCES, MC
    ZARNEGAR, R
    FASEB JOURNAL, 1993, 7 (04): : A637 - A637
  • [22] The activation of hepatocyte growth factor promoted hepatic stellate cells apoptosis via rho pathway
    Shen, Yanhua
    Jiang, Haixing
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2013, 28 : 829 - 829
  • [23] The activation of hepatocyte growth factor promoted hepatic stellate cells apoptosis via rho pathway
    Hua, Shenyan
    Xing, Jianghai
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2013, 28 : 830 - 830
  • [24] Insulin-like growth factor signaling pathways in rat hepatic stellate cells: Importance for DNA synthesis and hepatocyte growth factor production
    Skrtic, S
    Wallenius, K
    Gressner, AM
    Jansson, JO
    JOURNAL OF HEPATOLOGY, 2000, 32 : 84 - 84
  • [25] Induction of hepatocyte growth factor (HGF) in rat microglial cells by prostaglandin E2
    Zhang, LL
    Himi, T
    Murota, SI
    JOURNAL OF NEUROSCIENCE RESEARCH, 2000, 62 (03) : 389 - 395
  • [26] Hepatocyte growth factor (HGF) inhibits hepatocyte apoptosis in a mouse model of cholestasis
    Li, Z
    Mizuno, S
    Schuppan, D
    Nakamura, T
    JOURNAL OF HEPATOLOGY, 2004, 40 : 87 - 88
  • [27] HEPATOCYTE GROWTH-FACTOR (HGF) INDUCED GENE-EXPRESSION IN LIVER-CELLS
    ARIZTIA, EV
    IYER, AP
    FASEB JOURNAL, 1995, 9 (03): : A2 - A2
  • [28] Hepatocyte growth factor scatter factor (HGF/SF) induces vascular permeability factor (VPF/VEGF) expression by cultured keratinocytes
    Gille, J
    Khalik, M
    König, V
    Kaufmann, R
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1998, 111 (06) : 1160 - 1165
  • [29] Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and characterization of HGF receptor cDNA
    Ville Raymond Wallenius
    Helén Rawet
    Stanko Skrtic
    Khalil Helou
    Yan Qiu
    Göran Levan
    Staffan Ekberg
    Björn Carlsson
    Olle Gustave Petrus Isaksson
    Toshikazu Nakamura
    John-Olov Jansson
    Mammalian Genome, 1997, 8 : 661 - 667
  • [30] Met. hepatocyte growth factor scatter factor (HGF/SF) expression in mesotheliomas
    Shen, R
    Bui, H
    Resau, J
    LABORATORY INVESTIGATION, 1999, 79 (01) : 186A - 186A