Hepatocyte Growth Factor Facilitates Colonic Mucosal Repair in Experimental Ulcerative Colitis in Rats

Tahara, Yoshihiro; Ido, Akio; Yamamoto, Shojiro; Miyata, Yukio; Uto, Hirofumi; Hori, Takeshi; Hayashi, Katsuhiro; Tsubouchi, Hirohito

doi:10.1124/jpet.103.054106

Cited by 93 publications

(89 citation statements)

References 40 publications

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“…It is induced by tumor necrosis factor (TNF)-α and IL-1β activation and is characterized by neutrophil mucosal infiltration (4,9). Most rodent models of UC based on DSS administration employ concentrations between 3% and 7% DSS in drinking water (13,(17)(18)(19)(20)(21)(22) In our study, after 8 days of 5% DSS administration in all groups, the colonic mucosa appeared hyperemic, edematous with hemorrhagic erosions and tiny blood coagula. The body weight decreased gradually and the animals exhibited diarrhea and hematochezia.…”

Section: Discussionmentioning

confidence: 61%

“…DSS induced UC in rats is a well-established model of inflammatory bowel disease, which is clinically and histologically similar to human UC (12,13). It is induced by tumor necrosis factor (TNF)-α and IL-1β activation and is characterized by neutrophil mucosal infiltration (4,9).…”

Section: Discussionmentioning

confidence: 99%

“…An experimental model of UC is induced in rodents by the administration of dextran sulfate sodium (DSS) in the drinking water (12). The DSS-induced colitis causes to the rodents to exhibit many symptoms characteristic of human UC, including bloody feces, diarrhea and weight loss, as well as histopathological lesions characteristic of human UC, including mucosal ulceration and shortening of the large intestine (12,13). DSS-induced UC in Wistar rats has been used widely as an experimental model and appears to mimic nearly all of the morphological characteristics and lesion distributions with human UC.…”

Section: Introductionmentioning

confidence: 99%

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Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration

Varnalidis

Ioannidis

Karamanavi

et al. 2011

Rev. esp. enferm. dig.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration

Varnalidis

Ioannidis

Karamanavi

et al. 2011

Rev. esp. enferm. dig.

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“…Another growth factor, HGF, is secreted from stromal cells during inflammation and activated by HGF activator, which is activated by thrombin in injured tissues. This growth factor promotes proliferation, activation, and differentiation of intestinal endothelial and epithelial cells during angiogenesis and facilitates mucosal repair in experimental colitis (65,151). Additionally, bFGF is a heparin-binding protein involved in intestinal inflammation and it promotes angiogenesis through endothelial cell proliferation, migration, and differentiation, as well as proliferation of mesenchymal cells (67,154).…”

Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 99%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

145

114

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Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

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“…HGF activator and HGF activator inhibitor type-1, both HGF-associated molecules involved in the activation of HGF in injured tissues, are associated with colonic mucosal repair (9,10); HGF expression is increased in inflamed colonic mucosal tissues in patients with ulcerative colitis (11). We previously reported that systemic administration of recombinant human HGF ameliorated experimental colitis in rats (12,13). Perturbed homeostasis between luminal antigens (e.g., commensal bacteria) and mucosal immunity serves as a critical determinant in the development of gut inflammation in IBD.…”

Section: Introductionmentioning

confidence: 99%

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

Yamaji

Ido

Moriuchi³

et al. 2011

Oncol Rep

Self Cite

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Abstract. Hepatocyte growth factor (HGF), which facilitates the repair of injured mucosa, has the potential to be a new therapeutic agent for inflammatory bowel disease (IBD). However, given that the incidence of colorectal cancer increases continuously with disease duration in patients with IBD, the fact that HGF is a potent mitogen for intestinal epithelial cells may further heighten the risk of bowel cancer in this patient population. In this study, we examined the effects of recombinant HGF on colorectal cancer development in mice with or without experimentally induced colitis. Although HGF stimulated proliferation of colonic epithelial cells in normal mucosa, the development of colorectal cancer induced by repeated injection of azoxymethane (AOM) was significantly inhibited by HGF treatment. In a mouse model of colitis-associated cancer, colorectal cancer frequently developed despite only a single injection of AOM prior to three cycles of dextran sulfate sodium administration. However, HGF treatment significantly facilitated the repair of injured mucosa, leading to inhibition of colorectal cancer development in a dose-dependent manner. Thus, HGF-induced repair of injured mucosa inhibits rather than accelerates the development of colorectal cancer, and these results also suggest the importance of blocking the cycles of mucosal injury and repair to prevent colitis-associated colorectal cancer.

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Hepatocyte Growth Factor Facilitates Colonic Mucosal Repair in Experimental Ulcerative Colitis in Rats

Cited by 93 publications

References 40 publications

Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration

Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

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

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