Hepatocyte growth factor ameliorates mucosal injuries leading to inhibition of colon cancer development in mice

Yamaji, Naohisa; Ido, Akio; Moriuchi, Akihiro; Numata, Masatsugu; Setoyama, Hitoshi; Tamai, Tsutomu; Funakawa, Keita; Fujita, Hiroshi; Sakiyama, Toshio; Uto, Hirofumi; Oketani, Makoto; Tsubouchi, Hirohito

doi:10.3892/or.2011.1294

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…Severity of colon inflammation is a risk factor for colorectal neoplasia in ulcerative colitis6162. HGF ameliorates mucosal injuries leading to inhibition of colon cancer development in mice63. These reports suggest that chronic mucosal inflammation promotes colitis associated colon cancer growth.…”

Section: Discussionmentioning

confidence: 93%

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation

Takahashi

Yoshimura

Ohkura

et al. 2016

Sci Rep

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Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naïve Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2-deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.

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Section: Discussionmentioning

confidence: 93%

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation

Takahashi

Yoshimura

Ohkura

et al. 2016

Sci Rep

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“…HGF is a potent mitogen and motogen for various epithelial cells [20, 21]. It is produced following HCl- or bleomycin-induced acute lung injury and plays a role in pulmonary epithelial cell regeneration [22, 23].…”

Section: Discussionmentioning

confidence: 99%

The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury

Yang

et al. 2016

Respir Res

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BackgroundOrgan regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown.MethodsBased on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells.ResultsThe results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair. Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo. It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation.ConclusionsAEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.

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Hepatocyte Growth Factor Facilitates Esophageal Mucosal Repair and Inhibits the Submucosal Fibrosis in a Rat Model of Esophageal Ulcer

et al. 2018

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Background/Aims: Esophageal mucosal damage often causes scar tissue, leading to refractory stricture. The aim of this study was to clarify the effect of hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading to stricture in a rat model of esophageal ulcer. Methods: Esophageal ulcers were induced in rats by topical exposure of the lower esophageal serosa to acetic acid, followed by intraperitoneal administration of HGF (200 µg/day) using an osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was investigated macroscopically and microscopically. The effect of HGF on epithelial cell proliferation and the expression of genes closely associated with the development of fibrosis were also examined. Results: The administration of HGF for 7 days led to a significant reduction in the ulcerative area and enhanced the proliferation of esophageal epithelial cells. HGF treatment significantly decreased the fibrosis, and subsequently attenuated not only the foreshortening but also the narrowing of the esophagus. The expression levels of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)-2, -9 were significantly decreased among rats treated with HGF. Conclusion: HGF facilitates the repair of esophageal mucosal injury and may also ameliorate the esophageal fibrosis, possibly through enhanced re-epithelization.

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Hepatocyte growth factor ameliorates mucosal injuries leading to inhibition of colon cancer development in mice

Cited by 6 publications

References 33 publications

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation

The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury

Hepatocyte Growth Factor Facilitates Esophageal Mucosal Repair and Inhibits the Submucosal Fibrosis in a Rat Model of Esophageal Ulcer

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