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

Ido, Akio; Numata, Masatsugu; Kodama, Mayumi; Tsubouchi, Hirohito

doi:10.1007/s00535-005-1705-x

Cited by 63 publications

(58 citation statements)

References 76 publications

(76 reference statements)

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“…HGF has also been shown to be upregulated during IBD. Interestingly, administration of human HGF and HGF gene therapy decrease disease severity in experimental colitis, an effect that is opposite of that of most growth factors during IBD (13,62). These data combined with the VEGF data indicates growth factors as primary mediators of inflammation induced angiogenesis in experimental and human IBD.…”

Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 87%

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

143

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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Section: Angiogenic Mediators In Ibd and Experimental Colitismentioning

confidence: 87%

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

143

114

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“…No mRNA for the FGF7 gene was detected in colon of dextran sodium sulfate challenged pigs (another model of IBD) fed a control diet or diets supplemented with n − 3 PUFA (no data was available for n − 6 PUFA) despite increased colonic tissue regeneration [43]. This result indicates that epithelial regeneration may in this case be FGF7-independent although its occurrence might depend on other growth factors and cytokines [44]. In the Bassaganya-Riera and Hontecillas study [43], an n − 3 PUFA-enriched diet failed to protect from IBD, and instead promoted remission from IBD possibly by activating PPAR␦.…”

Section: Discussionmentioning

confidence: 99%

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

Roy

Barnett

Knoch

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acidand arachidonic acid-enriched diets AbstractIn vivo models of Inflammatory Bowel Diseases (IBD) elucidate important mechanisms of chronic inflammation. Complex intestinal responses to food components create a unique "fingerprint" discriminating health from disease. Five-week-old IL10−/− and C57BL/6J (C57; control) mice were inoculated orally with complex intestinal microflora (CIF) and/or pure cultures of Enterococcus faecalis and E. faecalis (EF) aiming for more consistent inflammation of the intestinal mucosa. Inoculation treatments were compared to noninoculated IL10−/− and C57 mice, either kept in specific pathogen free (SPF) or conventional conditions (2×5 factorial design). At 12 weeks of age, mice were sacrificed for intestinal histological (HIS) and transcriptomic analysis using limma and Ingenuity Pathway Analysis Software. Colonic HIS was significantly affected (P < 0.05) in inoculated IL10−/− mice and accounted for approximately 60% of total intestinal HIS. Inoculation showed a strong effect on colonic gene expression, with more than 2000 genes differentially expressed in EF·CIF-inoculated IL10−/− mice. Immune response gene expression was altered (P < 0.05) in these mice. The second study investigated the effect of arachidonic (AA) and eicosapentaenoic acid (EPA) on colonic HIS and gene expression to test whether EPA, contrary to AA, diminished intestinal inflammation in EF·CIF IL10−/− mice (2×4 factorial design). AIN-76A (5% corn oil) and AIN-76A (fat-free) +1% corn oil supplemented with either 3.7% oleic acid (OA), AA or EPA were used. IL10−/− mice fed EPA-and AAenriched diets had at least 40% lower colonic HIS (P < 0.05) than those fed control diets (AIN-76A and OA diets). The expression of immune response and 'inflammatory disease' genes (down-regulated: TNF, IL6, S100A8, FGF7, PTGS2; up-regulated: PPAR, MGLL, MYLK, PPSS23, ABCB4 with EPA and/or AA) was affected in IL10−/−mice fed EPA-and AA-enriched diets, compared to those fed AIN-76A diet. AbstractIn vivo models of Inflammatory Bowel Diseases (IBD) elucidate important mechanisms of chronic inflammation. Complex intestinal responses to food components create a unique "fingerprint" discriminating health from disease. Five-week-old IL10 −/− and C57BL/6J (C57; control) mice were inoculated orally with complex intestinal microflora (CIF) and/or pure cultures of Enterococcus faecalis and E. faecalis (EF) aiming for more consistent inflammation of the intestinal mucosa. Inoculation treatments were compared to non-inoculated IL10 −/− and C57 mice, either kept in specific pathogen free (SPF) or conventional conditions (2 × 5 factorial design). At 12 weeks of age, mice were sacrificed for intestinal histological (HIS) and transcriptomic analysis using limma and Ingenuity Pathway Analysis Software. Colonic HIS was significantly affected (P < 0.05) in inoculated IL10 −/− mice and accounted for approximately 60% of total ...

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“…Third, although admittedly still debated in terms of prevalence, individuals with autism can present complex medical profiles, such as gastrointestinal, immune, and nonspecific neurological dysfunctions (14,15). In addition to brain development, the pleiotropic MET receptor tyrosine kinase has specific roles in digestive system development and repair (18,23,24) and modulation of T cell-activated peripheral monocytes and dendritic antigen-presenting cells (20,22). We raise the possibility, still to be tested, that increased risk for autism, due to a functional polymorphism in the MET gene, may impart in certain individuals shared etiology of a parallel, although independent, disruption of brain and peripheral organ development and function.…”

Section: Discussionmentioning

confidence: 99%

“…MET is best understood for its role in the metastasis of a variety of cancers (16), due to somatic gain-of-function mutations, and in mediating hepatocyte growth factor (HGF)͞scatter factor signaling in peripheral organ development and repair (17)(18)(19). MET signaling contributes to immune function (20)(21)(22) and gastrointestinal repair (18,23,24). Recent studies by our group and others revealed that MET also contributes to development of the cerebral cortex (25,26) and cerebellum (27), both of which exhibit developmental disruptions in autism (28,29).…”

mentioning

confidence: 99%

A genetic variant that disrupts MET transcription is associated with autism

Campbell¹,

Sutcliffe

Ebert³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

387

352

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There is strong evidence for a genetic predisposition to autism and an intense interest in discovering heritable risk factors that disrupt gene function. Based on neurobiological findings and location within a chromosome 7q31 autism candidate gene region, we analyzed the gene encoding the pleiotropic MET receptor tyrosine kinase in a family based study of autism including 1,231 cases. MET signaling participates in neocortical and cerebellar growth and maturation, immune function, and gastrointestinal repair, consistent with reported medical complications in some children with autism. Here, we show genetic association (P ‫؍‬ 0.0005) of a common C allele in the promoter region of the MET gene in 204 autism families. The allelic association at this MET variant was confirmed in a replication sample of 539 autism families (P ‫؍‬ 0.001) and in the combined sample (P ‫؍‬ 0.000005). Multiplex families, in which more than one child has autism, exhibited the strongest allelic association (P ‫؍‬ 0.000007). In case-control analyses, the autism diagnosis relative risk was 2.27 (95% confidence interval: 1.41-3.65; P ‫؍‬ 0.0006) for the CC genotype and 1.67 (95% confidence interval: 1.11-2.49; P ‫؍‬ 0.012) for the CG genotype compared with the GG genotype. Functional assays showed that the C allele results in a 2-fold decrease in MET promoter activity and altered binding of specific transcription factor complexes. These data implicate reduced MET gene expression in autism susceptibility, providing evidence of a previously undescribed pathophysiological basis for this behaviorally and medically complex disorder.autism spectrum disorder ͉ association ͉ candidate gene ͉ hepatocyte growth factor ͉ hepatocyte growth factor receptor

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

Cited by 63 publications

References 76 publications

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

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

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

A genetic variant that disrupts MET transcription is associated with autism

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