Partial purification of rat hepatic stimulator substance and characterization of its action on hepatoma cells and normal hepatocytes

Fleig, Wolfgang E.; Hoss, Gerhard

doi:10.1002/hep.1840090213

Cited by 48 publications

(36 citation statements)

References 33 publications

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“…In this study, HSS was partially purified and its molecular size was likety to ca. 15 kD, which was consistent with the report of Fleig and co-worker [3]. It was also demonstrated in this experiment for the first time that HSS increased EGF specific binding to its receptors and such increase was apparently caused by the enhancement of receptor internalization.…”

Section: Discusionsupporting

confidence: 93%

“…The animals were killed by cervical dislocation and the livers were removed immediately. HSS was extracted according to the method described by LaBrecque [7] and Fleig [3]. Briefly, the livers were flushed with Dulbecco'b phosphate-buffered saline (PBS, pH 7.4) via the portal vein, weighed and homogenated to 35% in PBS (w/v).…”

Section: Hss Preparation and Purificationmentioning

confidence: 99%

“…After a subtotal resection of adult rat liver, the remnant liver commenced to proliferate dramatically if the cytosol extract from weanling rat liver was administrated to the hepatectomized rats [19]. Since then, much effort toward the identification, purification and characterization of this growth-induced substance has been made [2,3,5]. Despite of these, however, little is known about the mechanisms of HSS action on hepatocytes.…”

Section: Discusionmentioning

confidence: 99%

“…HSS, upon acting on hepatocytes and through a so-far unknown mechanism, stimulates the cell DNA synthesis [2], [3], promotes the cell proliferation and even more alleviates liver injuries induced by CCl 4 and D-galactosamine in mice [4]. Although the importance of HSS in the regulation of liver regeneration is well recognized, the mechanism by which HSS acts on hepatocytes remain still unclear.…”

Section: Introductionmentioning

confidence: 99%

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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: Discusionsupporting

confidence: 93%

Section: Hss Preparation and Purificationmentioning

confidence: 99%

Section: Discusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Interestingly, the stimulating effect of rhHPPCn on L02 was lower than that on SMMC7721 (P Ͻ 0.05), a finding that is similar to prior findings in studies of HSS. 19 The specificity of the activity of rhHPPCn in different cell types is shown in Fig. 3B.…”

Section: Effect Of Rhhppcn On Cell Growth and Proliferation In Vitromentioning

confidence: 97%

Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn

Chu¹,

Zhang²,

Shi³

et al. 2008

Hepatology

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Hepatic stimulating substance (HSS) was first isolated from weanling rat liver in 1975 and found to stimulate hepatic DNA synthesis both in vitro and in vivo. Since then, mammalian and human HSS have been investigated for their potential to treat hepatic diseases. However, the essential nature in composition and structure of HSS remain puzzling because HSS has not been completely purified. Heating, ethanol precipitation, and ion-exchange chromatographies had been carried out to isolate the protein with specific stimulating activity from newborn calf liver, and [ 3 H]thymidine deoxyribose (TdR)/bromodeoxyuridine (BrdU) incorporation and carboxyfluorescein diacetate succinimidyl ester (CFSE)-based proliferation assay to determine the bioactivity in vitro and in vivo. We report the purification of a novel 30-kDa protein from a crude extract of calf liver HSS. This protein is a member of the leucine-rich acidic nuclear protein family (LANP) and has been named hepatopoietin Cn (HPPCn). Studies of partially hepatectomized (PH) mice show that levels of HPPCn messenger RNA (mRNA) increase after liver injury. Furthermore, the recombinant human protein (rhHPPCn) was shown to stimulate hepatic DNA synthesis and activate signaling pathways involved in hepatocyte proliferation in vitro and in vivo. Conclusion: HPPCn is a novel hepatic growth factor that plays a role in liver regeneration. (HEPATOLOGY 2008;47:986-995.)

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Comitogenic effects of vasoactive intestinal polypeptide on rat hepatocytes

1996

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The primary mitogens such as epidermal growth factor and transforming growth factor-alpha are known to stimulate DNA synthesis in primary cultures of adult rat hepatocytes. Vasoactive intestinal polypeptide (VIP) was found to amplify DNA synthesis induced by the primary mitogens and thus acted as a comitogen. The comitogenic effect of VIP was specific for the culture medium, suggesting that minor components in the medium were required for hepatocytes to fully respond to VIP. Glutamic acid is probably one of these minor components, although other components present in the nutrient-rich medium were also necessary for the full comitogenic effect. Other comitogens such as insulin, vasopressin, and angiotensin II interacted additively with low concentrations of VIP. The comitogenic effect of VIP was also found in hepatocytes cultured from regenerating rat liver after a partial hepatectomy. In the regenerating hepatocyte cultures, VIP can act as a mitogen even in the absence of the primary mitogen EGF. VIP mRNA was found in several organs including brain, intestine, and liver, and its expression was slightly induced in liver 24 h after a partial hepatectomy. These results suggest that VIP can act as a hepatic comitogen and may play a role in liver cell proliferation.

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Partial purification of rat hepatic stimulator substance and characterization of its action on hepatoma cells and normal hepatocytes

Cited by 48 publications

References 33 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

Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn

Comitogenic effects of vasoactive intestinal polypeptide on rat hepatocytes

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