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Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice.
Hepatology 1999; 30(1):151-9Hep

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 micrograms 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.

Authors+Show Affiliations

Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10385651

Citation

Kosai, K, et al. "Hepatocyte Growth Factor Prevents Endotoxin-induced Lethal Hepatic Failure in Mice." Hepatology (Baltimore, Md.), vol. 30, no. 1, 1999, pp. 151-9.
Kosai K, Matsumoto K, Funakoshi H, et al. Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice. Hepatology. 1999;30(1):151-9.
Kosai, K., Matsumoto, K., Funakoshi, H., & Nakamura, T. (1999). Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice. Hepatology (Baltimore, Md.), 30(1), pp. 151-9.
Kosai K, et al. Hepatocyte Growth Factor Prevents Endotoxin-induced Lethal Hepatic Failure in Mice. Hepatology. 1999;30(1):151-9. PubMed PMID: 10385651.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatocyte growth factor prevents endotoxin-induced lethal hepatic failure in mice. AU - Kosai,K, AU - Matsumoto,K, AU - Funakoshi,H, AU - Nakamura,T, PY - 1999/7/1/pubmed PY - 1999/7/1/medline PY - 1999/7/1/entrez SP - 151 EP - 9 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 30 IS - 1 N2 - 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 micrograms 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. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/10385651/Hepatocyte_growth_factor_prevents_endotoxin_induced_lethal_hepatic_failure_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270913999003213 DB - PRIME DP - Unbound Medicine ER -