Administration of rhHGF-Activator Via Portal Vein Stimulates the Regeneration of Cirrhotic Liver After Partial Hepatectomy in Rats1

Yanagida, Hidesuke; Kaibori, Masaki; Hijikawa, Takeshi; Kwon, A‐Hon; Kamiyama, Yasuo; Okumura, Tadayoshi

doi:10.1016/j.jss.2005.08.002

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…Additionally, HGFA inhibitor (HAI)-1, which was first purified as an inhibitor of HGFA (36), regulates HGFA activity at sites of tissue injury (37). Recently, Yanagida et al reported that the administration of recombinant human HGFA stimulated the regeneration of cirrhotic liver after partial hepatectomy through the activation of endogenous pro-HGF (38). In the present study, we administered rh-HGF (0.3 mg/kg) in an already active heterodimeric form into cirrhotic rats once a day for 4 weeks (group H1) or twice a day for the last 2 weeks (group H2) of a 4-week DMN treatment.…”

Section: Discussionmentioning

confidence: 99%

Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats

Kusumoto

Ido²,

Moriuchi³

et al. 2006

Int J Mol Med

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Abstract. Hepatocyte growth factor (HGF) is a promising agent for the treatment of liver cirrhosis because of its mitogenic and anti-fibrotic effects. We investigated the effect of recombinant human HGF (rh-HGF) on cirrhosis development; its pharmacokinetics and nephrotoxicity in rats with liver cirrhosis induced by 4-week treatment with dimethylnitrosamine (DMN). rh-HGF (0.3 mg/kg) was intravenously administered to rats once a day for 4 weeks in parallel with DMN treatment or twice a day for the last 2 weeks of DMN treatment. Repeated doses of rh-HGF increased the liver weight and serum albumin, and reduced serum ALT. The development of hepatic fibrosis was inhibited more efficiently by extended low-dose treatment with rh-HGF. In cirrhotic rats, serum levels of rh-HGF increased and clearance was decreased, leading to an increase in the area under the plasmaconcentration time curve and a decrease in the steady-state volume of distribution. Repeated doses of rh-HGF led to increased urinary albumin excretion, but no rh-HGF-treated animals developed increased serum creatinine levels. Urinary albumin excretion returned to baseline after the cessation of rh-HGF. These results suggest that extended treatment with rh-HGF is required for the attenuation of cirrhosis, and repeated doses of rh-HGF cause adverse effects in extra-hepatic organs. These issues must be resolved before the widespread application of rh-HGF in the treatment of liver cirrhosis.

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Section: Discussionmentioning

confidence: 99%

Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats

Kusumoto

Ido²,

Moriuchi³

et al. 2006

Int J Mol Med

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“…Among these proteases, HGF activator (34 kDa) is the most efficient at converting proHGF into mature HGF (59). Both the liver and, to a lesser extent, gastrointestinal tissue synthesize HGF activator (60, 61). Following translation, this protease circulates as an inactive precursor, activator proHGF (96 kDa), and is activated upon thrombin cleavage (62).…”

Section: Structure and Molecular Biology Of Hgf And Its Receptor (C-met)mentioning

confidence: 99%

The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes

et al. 2018

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In obesity, insulin resistance (IR) and diabetes, there are proteins and hormones that may lead to the discovery of promising biomarkers and treatments for these metabolic disorders. For example, these molecules may impair the insulin signaling pathway or provide protection against IR. Thus, identifying proteins that are upregulated in IR states is relevant to the diagnosis and treatment of the associated disorders. It is becoming clear that hepatocyte growth factor (HGF) is an important component of the pathophysiology of IR, with increased levels in most common IR conditions, including obesity. HGF has a role in the metabolic flux of glucose in different insulin sensitive cell types; plays a key role in β-cell homeostasis; and is capable of modulating the inflammatory response. In this review, we discuss how, and to what extent HGF contributes to IR and diabetes pathophysiology, as well as its role in cancer which is more prevalent in obesity and diabetes. Based on the current literature and knowledge, it is clear that HGF plays a central role in these metabolic disorders. Thus, HGF levels could be employed as a biomarker for disease status/progression, and HGF/c-Met signaling pathway modulators could effectively regulate IR and treat diabetes.

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“…Kaibori et al reported that liver regeneration in the cirrhotic liver was impaired due to lack of proper HGF activation 51. They also showed that this impaired liver regeneration was restored by rhHGFA administration 52. In such a case, HGFA administration therapy may be more preferable, and anti-PCI antibody treatment could play a supportive role.…”

Section: Discussionmentioning

confidence: 99%

Protein C inhibitor regulates hepatocyte growth factor activator-mediated liver regeneration in mice

Hamada

Kamada

Hayashi

et al. 2008

Gut

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Administration of rhHGF-Activator Via Portal Vein Stimulates the Regeneration of Cirrhotic Liver After Partial Hepatectomy in Rats1

Cited by 8 publications

References 32 publications

Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats

Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats

The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes

Protein C inhibitor regulates hepatocyte growth factor activator-mediated liver regeneration in mice

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