Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis

Abstract

Liver cirrhosis is characterized by the hyper-accumulation Liver fibrosis/cirrhosis is characterized by hyper-accumulaof connective tissue components in the liver and is often tion of fibrous tissue components and is commonly observed accompanied by hypo-albuminemia, ascites, and esophageal in later or terminal states of chronic hepatic diseases. In ongovarices. In a prolonged stage, severe hepatic failure, or hepaing work, we found that the administration of human recombitocellular carcinoma, can occur. Chronic hepatic injuries nant hepatocyte growth factor (hrHGF) suppressed the onset caused by drugs, chemicals, alcohol abuse, or viral infections of liver fibrosis/cirrhosis in several distinct models and accelare predominant pathogenic causes for cirrhosis. Although erated the recovery from liver fibrosis/cirrhosis in rats. Rethe pathogenic mechanisms of cirrhosis are not fully underpeated administration of porcine serum for 10 weeks to rats stood, the over-production of extracellular matrices in the induced liver fibrosis without any accompanying hepatocelluliver, as well as of chronic parenchymal hepatocellular injury, lar injuries; in addition, the intravenous (i.v.) administration are likely to initiate the onset of cirrhosis. Therefore, preferof hepatocyte growth factor (HGF) to these rats suppressed ential hepatocellular replication and cytoprotection against increases in fibrous components and hydroxyproline contents hepatic injuries, as well as the stimulation of degradation in the liver, thus preventing the onset of liver fibrosis. Reand remodeling of extracellular fibrous components, seems peated administration of dimethylnitrosamine (DMN) for four to inhibit the onset or progress of hepatic fibrosis/cirrhosis. weeks induced liver cirrhosis, as characterized by the hyperSeveral lines of studies have shown that hepatocyte growth accumulation of fibrous components, infiltration of mononufactor (HGF), originally purified as a potent mitogen for rat clear leukocytes, and hepatic dysfunction. When HGF was hepatocytes, 1-3 is the long-sought hepatotrophic factor for injected daily for four weeks along with DMN-treatment, the liver regeneration. [4][5][6][7] Following the onset of various types of onset of DMN-induced hepatic fibrosis/cirrhosis was suphepatic injuries, HGF messenger RNA expression is rapidly pressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver up-regulated in the livers of experimental animals. 8,9 Serum were decreased. When HGF was injected for two weeks fol-HGF levels are elevated in patients with various hepatic dislowing four weeks of DMN-treatment, HGF accelerated the orders. 10,11 Extensive in vivo studies on the efficacy of recomrecovery from liver cirrhosis and prevented death due to he-binant HGF on hepatic regeneration revealed that HGF elicits patic dysfunction. Likewise, HGF-injection suppressed the on-a potent hepatotrophic action. HGF strongly stimulates DNA set of liver fibrosis, when liver fibrosis had be...

Subcutaneous adipose tissue–derived stem cells facilitate colonic mucosal recovery from 2,4,6-trinitrobenzene sulfonic acid (TNBS)–induced colitis in rats

“…In addition, one advantage of ADSCs is their potential to secrete growth factors, such as VEGF, HGF,20 and adiponectin,21 which facilitate the regeneration of injured tissue alone or synergistically 22. As has been reported, HGF regulates cell growth, motility, and morphogenesis of various types of cells, including epithelial cells and endothelial cells, and it also prevents fibrosis 23, 24. Recent studies have shown that the combination of HGF with VEGF increases neovascularization in the rat corneal assay25 and that HGF facilitates the repair of large colonic ulcers in TNBS‐induced colitis in rats 26.…”

Melatonin reduces dimethylnitrosamine‐induced liver fibrosis in rats

“…An effective treatment for liver fibrosis is still needed. Nevertheless, recent experimental studies have reported partial success against liver fibrosis in the DMN induced rats with hepatocyte growth factor [20], estradiol [6, 21], malotilate [22], halofuginone [23], retinyl palmitate [11], lipoic acid [24], interferon gamma [25], and sho‐saiko‐to, a Japanese herbal therapeutic [1, 26].…”

Hepatocyte growth factor and c‐Met expression in rat and human liver fibrosis

“…Furthermore, a decline in HGF expression levels during in vitro activation has been reported for rat HSC (9, 12). Significant effects of exogenously administered HGF on hepatocellular regeneration were also observed in vivo (13–18), and even antifibrotic activity has been attributed to a modified HGF in the rat model of DMN‐induced liver collapse (16). In consequence, substitution of HGF has been suggested to be of value in human liver disease including cirrhosis (18).…”