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Hepatocyte growth factor prevents endotoxin‐induced lethal hepatic failure in mice
Author(s) -
Kosai Kenichiro,
Matsumoto Kunio,
Funakoshi Hiroshi,
Nakamura Toshikazu
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300102
Subject(s) - hepatocyte growth factor , fulminant hepatic failure , apoptosis , sepsis , hepatocyte , medicine , in vivo , pharmacology , lipopolysaccharide , tumor necrosis factor alpha , liver injury , endocrinology , biology , transplantation , in vitro , receptor , liver transplantation , biochemistry , microbiology and biotechnology
Abstract Sepsis and endotoxemia are involved in the development of fulminant hepatic failure, the prognosis of which is extremely poor and the mortality is high, with no available effective therapy. Here, we report that hepatocyte growth factor (HGF) exerts potent antiapoptotic effects in vivo and effectively prevents endotoxin‐induced fulminant hepatic failure in mice. The animals were intraperitoneally injected three times with 120 μg human recombinant HGF or saline 6 hours and 30 minutes before and 3 hours after an intraperitoneal injection of lipopolysaccharide (LPS) and d ‐galactosamine (GalN). Administration of LPS + GalN, without HGF, rapidly led to massive hepatocyte apoptosis and severe liver injury, and all mice died of hepatic failure within 8 hours. In contrast, administration of human recombinant HGF strongly suppressed extensive progress of hepatocyte apoptosis and the liver injury induced by LPS + GalN, and 75% of the HGF‐treated mice survived. Moreover, HGF strongly induced Bcl‐xL expression and blocked apoptotic signal transduction upstream of CPP32 (caspase‐3) in the liver, thereby leading to inhibition of massive hepatocyte apoptosis. We suggest that HGF may well have the potential to prevent fulminant hepatic failure, at least through its potent antiapoptotic action.

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