Therapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice

Mukoyama, Tomoyuki; Kanbe, Takamasa; Murai, Rie; Murawaki, Yoshiyuki; Shimomura, Tokio; Hashiguchi, Koichi; Saeki, Toshiya; Ichiba, Miho; Yoshida, Yoko; Tanabe, Naotada; Kurimasa, Akihiro; Harada, Kiyoshi; Yashima, Kazuo; Hisatome, Ichiro; Ito, Hisao; Murawaki, Yoshikazu; Shiota, Goshi

doi:10.1016/j.bbrc.2005.01.166

Cited by 14 publications

(12 citation statements)

References 25 publications

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“…In addition to the duration of elevated serum HGF level, Arthur et al reported that there is a plateau above which a further increase in HGF levels provides no added benefit in HLA-B27 transgenic rats treated with recombinant HGF [21]. Recently, Mukoyama et al reported the therapeutic effect of adenoviral-mediated HGF gene administration via the intrarectal route on TNBS-induced colitis [39]. The method could transfect the gene successfully into the epithelial cells of the colon without elevation of serum HGF levels.…”

Section: Discussionmentioning

confidence: 94%

Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver

Hanawa

Suzuki

Kawauchi

et al. 2006

The Journal of Gene Medicine

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Section: Discussionmentioning

confidence: 94%

Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver

Hanawa

Suzuki

Kawauchi

et al. 2006

The Journal of Gene Medicine

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“…Several studies have reported that adenoviral-mediated, liposome-formulated, or naked HGF gene can be administered intrarectally, intramuscularly, or intravenously into an animal colitis model (8,14,20,25). Thus HGF gene therapy might be useful for the treatment of IBD.…”

mentioning

confidence: 97%

Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signaling

Kanayama

Takahara²,

Yata³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatocyte growth factor (HGF) can promote the regeneration of injured organs, including HGF gene therapy by electroporation (EP) for liver injury. In this study, we investigated the effect of HGF on dextran sulfate sodium-induced colitis and tried to clarify the regenerative mechanisms of colonic epithelial cells and the signaling pathway involved. Colitis was induced by dextran sulfate sodium in mice, together with HGF gene transfer by EP. On day 10, the colitis was evaluated histologically and by Western blot analysis. The colonic epithelial cell line MCE301 was exposed to HGF protein, and its proliferation and activated signaling pathway were analyzed. In vivo, the histological score improved and the number of Ki-67-positive epithelial cells increased in the HGF-treated mice compared with the controls. Western blot analysis showed enhanced expression of phospho-Akt in the HGF-treated mice compared with the controls. In vitro, HGF stimulated the proliferation of MCE301 cells. There was enhanced phospho-Akt expression for more than 48 h after HGF stimulation, although phospho-ERK1/2 was enhanced for only 10 min. LY-294002 or Akt small interfering RNA suppressed cell proliferation induced by HGF. Thus HGF induces the proliferation of colonic epithelial cells via the phosphatidylinositol 3-kinase/Akt signaling pathway. HGF gene therapy can attenuate acute colitis via epithelial cell proliferation through the PI3K/Akt pathway. These data suggested that HGF gene therapy by EP may be effective for the regeneration and repair of injured epithelial cells in inflammatory bowel disease.

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“…Ohda et al66 showed that the intraperitoneal administration of recombinant human HGF ameliorated DSSand TNBS-induced colitis through the inhibition of apoptosis, rather than by stimulating the proliferation of intestinal epithelial cells. Recently, Mukoyama et al67 demonstrated that the rectal administration of recombinant adenovirus expressing HGF facilitated the repair of TNBS-induced mucosal injuries, via both enhanced cell proliferation and the inhibition of epithelial-cell apoptosis.…”

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confidence: 99%

Mucosal repair and growth factors: recombinant human hepatocyte growth factor as an innovative therapy for inflammatory bowel disease

et al. 2005

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The repair of intestinal mucosal injuries is a tightly regulated process involving epithelial restitution, cell proliferation and maturation, and the dedifferentiation of epithelial cells. Deeper injuries also require additional repair mechanisms, including inflammatory processes, angiogenesis, and extracellular-matrix deposition. Once intestinal mucosal injury occurs, numerous growth factors and cytokines, including hepatocyte growth factor (HGF), keratinocyte growth factor, endothelial growth factor, epidermal growth factor, transforming growth factor-beta1, intestinal trefoil factor, interleukin (IL)-1, and IL-2, are induced in both the intestinal lumen and submucosa, and these factors cooperatively stimulate epithelial mucosal repair. HGF, a major agent promoting hepatocyte proliferation, also modulates intestinal epithelial cell proliferation and migration, leading to the acceleration of intestinal mucosal repair. Additionally, the proteolytic activation of HGF, which is mediated by HGF activator, is essential for the regeneration of injured intestinal mucosa. Recently, several studies have shown that the administration of recombinant human HGF or HGF gene therapy abrogates disease severity in several animal models of inflammatory bowel disease (IBD). Recombinant human HGF will soon be available for administration to patients with fulminant hepatic failure. Although additional preclinical biological studies are required, HGF has the potential to be an important new treatment modality promoting intestinal mucosal repair in patients with IBD.

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Therapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice

Cited by 14 publications

References 25 publications

Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver

Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver

Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signaling

Mucosal repair and growth factors: recombinant human hepatocyte growth factor as an innovative therapy for inflammatory bowel disease

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