Preventive effects of the deleted form of hepatocyte growth factor against various liver injuries

Masunaga, Hiroaki; Fujise, Nobuaki; Shiota, Akira; Ogawa, Hiromi; Satô, Yasushi; Imai, Eiichi; Yasuda, Hiroshi; Higashio, Kanji

doi:10.1016/s0014-2999(97)01485-4

Cited by 34 publications

(24 citation statements)

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“…A new class of drugs, broadly referred to as 'hepato-protectants', are showing considerable promise in pre-clinical and clinical studies, including hepatocyte growth factor (HGF), HGF deletion variants, and HGF synthetic mimetics (Kim et al, 2005;Ueki et al, 1999;Masunaga et al, 1998), as well as insulin-like growth factor (Sanz et al, 2005), and a small molecule caspase inhibitor that improves AST levels in patients with chronic HCV and is currently in clinical trials (Valentino et al, 2003). The exact mechanism of HGF's antifibrotic activity is uncertain, but may include inhibition of TGF␤ 1 activity and down-regulate of collagen gene expression (Inagaki et al, 2003).…”

Section: Reduce Inflammation and Immune Responsementioning

confidence: 99%

Hepatic fibrosis—Overview

2008

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Section: Reduce Inflammation and Immune Responsementioning

confidence: 99%

Hepatic fibrosis—Overview

2008

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“…It is a major agent promoting hepatocyte proliferation (9)(10)(11) and acts in concert with transforming growth factor (TGF)-· and heparinbinding epidermal growth factor during liver regeneration (12,13). Additionally, HGF ameliorates hepatic injury via anti-apoptotic effects in animal models of fulminant hepatic failure (14)(15)(16)(17)(18)(19)(20) and attenuates hepatic fibrosis in animals with liver cirrhosis (21)(22)(23)(24)(25). Consequently, HGF is considered to not only induce liver regeneration but also to inhibit disease progression and ameliorate hepatic fibrosis in patients suffering from intractable liver diseases.…”

Section: Introductionmentioning

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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“…dHGF is a glycoprotein of about 80 kDa and lacks 5 amino acids in the first kringle domain of the ␣ chain of HGF. It is a more potent mitogen than HGF for rat hepatocytes [8] and is effective in the preservation of liver function in a dosedependent manner in experimental hepatic injury models using liver resection or drugs [9,10]. HGF is also reported to be effective in regeneration of nonhepatic tissue, improving renal function in an experimental model of renal injury [11,12] and respiratory function in drug-induced experimental lung injury [13,14].…”

Section: Introductionmentioning

confidence: 99%