Induction of mitosis in primary cultures of adult rat hepatocytes under serum-free conditions

Hasegawa, Kaoru; Watanabe, Kazuto; Koga, Mutuyosi

doi:10.1016/0006-291x(82)91968-4

Cited by 82 publications

(41 citation statements)

References 16 publications

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“…It was reported that HSS alone had little effect on the DNA synthesis of the resting hepatocytes as in the primary culture hepatocytes, but in contrast, if combined with EGF, it could amplify the growth response of the cells to EGF both in vitro [20,21] and in vivo [22]. The EGF participation in the regulation of liver proliferation was demonstrated in the down-regulation of EGF receptor following partial hepatectomy [23].…”

Section: Discusionmentioning

confidence: 99%

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

Liu

Lei

et al. 1999

Cell Res

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The cytosolic liver-specific growth factor-hepatic stimulator substance (HSS) has been shown to be able to amplify the rat hepatocyte proliferation responded to EGF. In order to get more insight into the mechanism, the regulatory effect of HSS on EGF-receptor (EGF-R) and the receptor phosphorylation at molecular level was studied. HSS partially purified from weanling rat liver was given to cultured hepatocytes and its influence on EGF-R specific binding and internalization as well as mRNA expression were investigated. The results showed that preincubation of hepatocytes with HSS could lead to an increase in [ 125 I]-EGF binding to its receptors and inhibit EGFinduced receptor down-regulation. Furthermore, the over-expression of EGF-R mRNA stimulated by HSS was seen during 2-12 h after the incubation. Additionally, it was demonstrated with human hepatoma SMMC-7721 cells in Western blot that the EGF-R expression and the receptorautophosphorylation were increased with dose/time-dependency after HSS treatment . These results strongly suggest that the mechanism of HSS action on hepatocyte growth might be related to its modulation on EGF-R and receptor-mediated signaling transduction .

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Section: Discusionmentioning

confidence: 99%

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

Liu

Lei

et al. 1999

Cell Res

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“…Recently, several groups including ours found that adult rat hepatocytes in primary culture, which retain many of their in vivo liver functions, can proliferate when cultured at low density in medium containing insulin and epidermal growth factor (EGF) (1)(2)(3)(4)(5)(6). Thus, primary cultures of adult rat hepatocytes are a suitable in vitro system for use in studies on the humoral factor for hepatocyte growth.…”

mentioning

confidence: 99%

Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures.

Nakamura¹,

Teramoto²,

Ichihara³

1986

Proc. Natl. Acad. Sci. U.S.A.

545

315

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A growth factor (HGF) stimulating DNA synthesis of adult rat hepatocytes in primary culture was found in rat platelets. HGF was purified from rat platelets to homogeneity by a three-step procedure: stimulation of its release from platelets by thrombin, cation-exchanger fast protein liquid chromatography on a Mono S column, and heparin-Sepharose chromatography. HGF was clearly distinguishable from the platelet-derived growth factor (PDGF) by fast protein liquid chromatography. HGF was a heat-and acid-labile cationic protein that was inactivated by reduction with dithiothreitol. Its molecular mass was estimated to be 27 kDa by NaDodSO4/PAGE and its amino acid composition was very different from that of PDGF. The purified HGF stimulated DNA synthesis in adult rat hepatocytes at 2 ng/ml and was maximally effective at 20 ng/ml; its effect was additive or synergistic with those of insulin and EGF, depending on their combinations. HGF did not stimulate DNA synthesis of Swiss 3T3 cells, while PDGF did not stimulate that of hepatocytes. Thus, HGF showed clearly different cell specificity from PDGF in its growth-promoting activities. These findings indicate that HGF is a growth factor in platelets for mature hepatocytes.

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“…Mature rat hepatocytes in primary culture proliferate at low cell density in the presence of insulin and epidermal growth factor (EGF) (1)(2)(3)(4)(5). A density-dependent mechanism regulates entry of the cells into the cell cycle (1,3,4,6).…”

mentioning

confidence: 99%

Loss of reciprocal modulations of growth and liver function of hepatoma cells in culture by contact with cells or cell membranes.

Nakamura¹,

Nakayama²,

Teramoto³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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In mature rat hepatocytes in primary culture, many metabolic functions and cell growth are controlled reciprocally by cell density, and this reciprocal regulation is mediated by a cell-surface modulator through cell-cell contact. Cultured RY-121B cells from Reuber hepatoma and MH1Cj cells from Morris hepatoma, which retain some liverspecific functions, did not show any cell-density dependency of either cell growth or hepatocyte-specific functions, such as induction of tyrosine aminotransferase by dexamethasone. However, when RY-121B cells were cocultured with a low density of rat hepatocytes as monolayers in direct contact, they exerted contact-dependent control of DNA synthesis and of differentiated function of the hepatocytes. Furthermore, plasma membranes from various tumor cells including these hepatoma cells had strong modulator activity on primary cultures of normal rat hepatocytes, and their activity mimicked the reciprocal effects of cell density on DNA synthesis and induction of tyrosine aminotransferase. On the contrary, addition of plasma membranes from normal adult rat liver to sparse cultures of RY-121B or MH1Cj cells did not cause any inhibition of active DNA synthesis or enhancement of induction of tyrosine aminotransferase in these cells. These results suggest that hepatoma cells have lost cell density-dependent regulations of many cellular activities and cell growth because they have lost the ability to respond to the cell surface modulator, although they retain modulator activity on their plasma membranes.

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Induction of mitosis in primary cultures of adult rat hepatocytes under serum-free conditions

Cited by 82 publications

References 16 publications

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

Growth induction of hepatic stimulator substance in he-patocytes through its regulation on EGF receptors

Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures.

Loss of reciprocal modulations of growth and liver function of hepatoma cells in culture by contact with cells or cell membranes.

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