Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Francavilla, Antonella Bianca

doi:10.1016/0270-9139(91)90055-z

Cited by 39 publications

(75 citation statements)

References 28 publications

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“…These experiments support the feasibility of using a pharmacological approach as an alternative to hepatic resection for creation of a hyperplastic microenvironment conducive to gene insertion. For this purpose, T 3 is only one of several candidates -including hormones, growth factors and some of the most potent T -cell-directed immunosuppressive agents (4). The need to screen for such substances for their hepatic growth effect in intact animals as opposed to tissue culture conditions was emphasized before (4) and exemplified in the in vitro experiments of this report, in which T 3 alone was almost inert.…”

Section: Je 2£mentioning

confidence: 89%

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Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Francavilla¹

1994

Hepatology

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Subcutaneous injections of hormone triiodothyronine in rats resulted in peak blood levels at 24 hr with return to baseline by 96 hr. The injections stimulated a liver regeneration response that resembled in timing and in magnitude of DNA synthesis (peak, 24 hr) that induced by 40% hepatic resection. The principal proliferation was of hepatocytes. Although there were some temporal differences from the gene expression of transforming growth factor-a, transforming growth factor-~, and c-Ha-ras that are known to follow partial hepatectomy, the overall profile of these changes was similar to those after partial resection. The effect was liver specific and could be reproduced three times with no diminution in response in the same animal with injections at 10-day intervals. No response was detected in kidney or intestine. This effect in intact animals contrasted with the minimal ability of triiodothyronine to stimulate hepatocytes in culture. However, when the culture medium was enriched with epidermal growth factor, there was a dose-related response to triiodothyronine. The totality of these experiments provides a preliminary basis for the creation with pharmacological techniques of an in vivo hyperplastic hepatic condition permissive of transfection of new genes, as an alternative to partial hepatectomy. Although triiodothyronine was the test agent used, other hepatic growth factors singly or in combination could be candidates for this purpose.

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Section: Je 2£mentioning

confidence: 89%

“…T 3 also has modest hepatotrophic effects (4) that are identified in the Eck fistula screen model by the stimulation of proliferation and the prevention of hepatocyte atrophy (5). In this study, we further characterized the rat liver's response to T 3 including the mRNA to T 3 expression of the growth-associated genes TGF-a, TGF-f3 and cHa-ras.…”

mentioning

confidence: 95%

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Francavilla¹

1994

Hepatology

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“…Recently, these factors have also been called initiators, progressors, and augmentors [16], on the basis of the time of their intervention in the cell cycle (Fig. 2).…”

Section: Introductionmentioning

confidence: 99%

“…Hepatic stimulatory substance (HSS), cyclosporin A (CyA), FK 506, insulin, and insulinlike growth factor (IGF) II have been defined as augmentors [16][17][18][19][20]. They are not active in vitro, while in vivo they stimulate the proliferation of hepatocytes that have already completed the G 0 -G 1 transition.…”

Section: Introductionmentioning

confidence: 99%

Hepatic regeneration and growth factors

et al. 1993

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“…This operation is followed by tripling of hepatocyte proliferation, atrophy of hepatocytes within 4 days to about half their original volume and establishment of a new stable state after 4 days (2). Growth stimulating substances, when infused into the tied-off central portal vein after this operation, augment further the heightened proliferation of the Eck fistula liver and prevent liver atrophy after creation ofthe fistula (1,(3)(4)(5)(6)(7). These effects have been termed hepatotrophic.…”

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confidence: 99%

Effect on the canine Eck fistula liver of intraportal TGF-β alone or with hepatic growth factors

et al. 1992

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Transforming growth factor-p canceled the hepatocyte proliferation caused. by transforming growth factor-Of when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast. transforming growth factor-p had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor-2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected., but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor-a and transforming growth factor-p in the modulation of liver growth control. (HEPATOLOGY • q92; 16: 1267-1270 The Eck fistula (portacaval shunt) in dogs is a useful tool in the identification and study of hepatic growthmodulating substances, of which some of the most potent have little or no effect on hepatocytes in culture (1). This operation is followed by tripling of hepatocyte proliferation, atrophy of hepatocytes within 4 days to about half their original volume and establishment of a new stable state after 4 days (2). Growth stimulating substances, when infused into the tied-off central portal vein after this operation, augment further the heightened proliferation of the Eck fistula liver and prevent liver atrophy after creation ofthe fistula (1, 3-7). These effects have been termed hepatotrophic. In contrast, transforming growth factor-(3 (TGF-(3), a known inhibitor of hepatocyte proliferation in vitro (8,9), has the opposite effect in that it suppresses hepatocyte proliferation after creation of the Eck fistula and further reduces the size of the atrophied hepatocytes (1). The striking TGF-(3 effect is easily overridden with insulin (1).

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Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Cited by 39 publications

References 28 publications

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Hepatic regeneration and growth factors

Effect on the canine Eck fistula liver of intraportal TGF-β alone or with hepatic growth factors

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