Growth factor mRNA expression in normal colorectal mucosa and in uninvolved mucosa from ulcerative colitis patients

Chowdhury, A. K.; Fukuda, Ryo; Fukumoto, Shiro

doi:10.1007/bf02355024

Cited by 47 publications

(34 citation statements)

References 37 publications

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“…Thus, since we found a positive correlation between expression of the REG IV gene and that of the bFGF and HGF genes in the UC colonic mucosa, it appears likely that the enhanced expression of the REG IV gene is at least partly due to upregulation of bFGF and HGF in the mesenchymal cells. On the other hand, since the expression of the EGF receptor or other growth factor receptors may be upregulated in UC tissues, 3,6 not only growth factors but also their receptors are likely responsible for REG IV expression. In this context, as described above, we previously reported that cytokines such as IFN-g and IL-6 are responsible for the enhanced expression of REG Ia in the UC colonic mucosa.…”

Section: Effects Of Reg IVmentioning

confidence: 99%

“…[1][2][3][4][5] To regenerate the injured colonic tissues, growth factors are thought to play very important roles, and indeed, several growth factors are reported to be upregulated in the colonic tissues in UC. 3,6,7 However, few comprehensive studies have examined the expression patterns of various growth factors in UC tissues simultaneously, and the network of and the relationships among growth factors in UC tissues are not fully understood.Regenerating gene (REG) IV, the most recently discovered member of the REG gene family, was isolated from a cDNA library of UC tissues by Hartupee et al 8 Although the biological function of REG IV protein is still unclear, REG IV protein may play a role in cell growth because other REG family proteins have been shown to act as growth factors in gastrointestinal organs. 9-14 However, it still remains unknown whether the REG IV gene is indeed involved in the pathophysiology of UC and whether REG IV protein really functions as a growth factor.…”

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Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

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The regenerating gene (REG) IV gene was isolated from a cDNA library of ulcerative colitis (UC) tissues. However, its role in the pathophysiology of UC and subsequent development of colitic cancer is still unclear. We investigated the expression of the REG IV gene in UC and colitic cancer tissues and examined whether cytokines or growth factors are responsible for REG IV gene expression and whether REG IV gene induction affects cell growth and apoptosis in colon cancer cells. The expressions of REG IV and growth factor genes in UC tissues were analyzed by real time reverse transcription-polymerase chain reaction. The effects of cytokines and growth factors on REG IV gene expression were examined in SW403 cells by Northern blot analysis. The effects of REG IV gene induction on cell growth and H 2 O 2 -induced apoptosis were examined in DLD-1 cells by MTT and TUNEL assays, respectively. REG IV mRNA was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG IV mRNA expression was correlated with that of basic fibroblast growth factor (bFGF) as well as hepatocyte growth factor (HGF) mRNA expression in UC tissues. The REG IV gene expression in SW403 colon cancer cells was enhanced by stimulation with transforming growth factor-a, epidermal growth factor, bFGF, and HGF. REG IV gene induction promoted cell growth and conferred resistance to H 2 O 2 -induced apoptosis in DLD-1 cells. The REG IV gene is inducible by growth factors and may function as a growth promoting and/or an antiapoptotic factor in the pathophysiology of UC. The pathogenesis of ulcerative colitis (UC) is still unclear, but dysregulated immune function appears to be involved in its chronic inflammatory process, resulting in continuous damage of the colonic mucosa. [1][2][3][4][5] To regenerate the injured colonic tissues, growth factors are thought to play very important roles, and indeed, several growth factors are reported to be upregulated in the colonic tissues in UC. 3,6,7 However, few comprehensive studies have examined the expression patterns of various growth factors in UC tissues simultaneously, and the network of and the relationships among growth factors in UC tissues are not fully understood.Regenerating gene (REG) IV, the most recently discovered member of the REG gene family, was isolated from a cDNA library of UC tissues by Hartupee et al. 8 Although the biological function of REG IV protein is still unclear, REG IV protein may play a role in cell growth because other REG family proteins have been shown to act as growth factors in gastrointestinal organs. 9-14 However, it still remains unknown whether the REG IV gene is indeed involved in the pathophysiology of UC and whether REG IV protein really functions as a growth factor. Moreover, it has not been examined how REG IV gene expression is regulated. In the present study, therefore, in order to elucidate roles for REG IV in the pathophysiology of UC, we investigated the relationship between REG IV gene expression and clinicopat...

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Section: Effects Of Reg IVmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

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“…The role of HGF/SF in digestive tract disorders has not been as well characterized. Previous studies have shown that expression of HGF/SF and c-MET mRNA among UC and control patients was comparable (Chowdhury et al, 1996). In contrast, serum HGF/SF levels in patients with IBD were higher than those in healthy individuals (Matsuno et al, 1997).…”

Section: Discussionmentioning

confidence: 93%

Ulcerative Proctitis, Rectal Prolapse, and Intestinal Pseudo-Obstruction in Transgenic Mice Overexpressing Hepatocyte Growth Factor/Scatter Factor

Takayama

Takagi

LaRochelle

et al. 2001

Laboratory Investigation

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SUMMARY:Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of gastrointestinal epithelial cells in vitro;however, the physiological role of HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo function, mice were analyzed in which an HGF/SF transgene was overexpressed throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in this study (28 of 87) died by 6 months of age as a result of sporadic intestinal obstruction of unknown etiology. Enteric ganglia were not overtly affected, indicating that the pathogenesis of this intestinal lesion was different from that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse. Expression of interleukin-2 was decreased in the transgenic colon, indicating that HGF/SF may influence regulation of the local intestinal immune system within the colon. These results suggest that HGF/SF plays an important role in the development of gastrointestinal paresis and chronic intestinal inflammation. HGF/SF transgenic mice may represent a useful model for the study of molecular mechanisms associated with a subset of IBD and intestinal pseudo-obstruction. Moreover, our data identify previously unappreciated side effects that may be encountered when using HGF/SF as a therapeutic agent. (Lab Invest 2001, 81:297-305).H epatocyte growth factor/scatter factor (HGF/ SF) was first identified as a highly potent hepatocyte mitogen (Gohda et al, 1988;Nakamura et al, 1989) but is now known as a multifunctional cytokine based on its ability to stimulate proliferation, movement, and/or morphogenesis of a broad spectrum of cultured epithelial cells expressing the tyrosine kinase receptor encoded by the c-met proto-oncogene (Gherardi and Stoker, 1991;Montesano et al, 1991;Rosen et al, 1994;Rubin et al, 1991;Vande Woude, 1992;Zarnegar and Michalopoulos, 1995). HGF/SF is produced in cells of mesenchymal origin, whereas c-met is expressed in adult and embryonic epithelium, implicating HGF/SF-Met signal transduction pathways as important in the epithelial-mesenchymal interaction that occurs during embryogenesis, tissue organization, and organogenesis. Gene targeting studies have shown that HGF/SF-Met signaling is required for the normal development of liver, skeletal muscle, and placenta Schmidt et al, 1995;Uehara et al, 1995).In the fetal digestive tract, c-met transcripts were found in the epithelia of the intestinal anlagen and the villi, whereas the distribution of HGF/SF RNA showed dynamic changes during mouse development by in situ hybridization (Sonnenberg et al, 1993). Immunohistochemical analysis of temporal expression revealed that both HGF/SF and c-Met could be detected between 7 and 8 weeks of gestation in human fetal digestive tissues (Kermorgant et al, 1997). These results suggest that HGF/SF-Met signaling participates in digestive system morphogenesis. Moreover, previous studies demonstrated that HGF/SF can stimulate both esophageal ...

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“…These factors mediate the biological functions of epithelial and mesenchymal cells through EGF receptors (EGFRs) (1). Several studies have demonstrated that the EGF family and the EGFR signalling pathway play a crucial role in the regenerative response of the mucosal damage in the gastrointestinal tract (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Amphiregulin and epiregulin expression in neoplastic and inflammatory lesions in the colon

Nishimura

Andoh²,

Inatomi³

et al. 2008

Oncol Rep

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Abstract. Amphiregulin and epiregulin belong to the epidermal growth factor family and mediate the biological functions of epithelial and mesenchymal cells through epidermal growth factor receptors. In this study, we evaluated the amphiregulin and epiregulin expression in neoplastic and inflammatory lesions from the human colon. Surgicallyobtained specimens were stained using standard immunohistochemical procedures. Amphiregulin and epiregulin were not expressed in the normal colonic mucosa, but were clearly detectable in adenomas and carcinomas. Weak immunostaining was also detected in mesenchymal cells from the tumor tissues. In the active mucosa of patients with ulcerative colitis and Crohn's disease, amphiregulin was mainly expressed by the epithelial cells. In addition, positive immunostaining was also detectable in the surrounding mesenchymal cells. In conclusion, amphiregulin and epiregulin may play important roles in colonic tumor growth and mucosal repair in the inflamed mucosa of inflammatory bowel disease.

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Growth factor mRNA expression in normal colorectal mucosa and in uninvolved mucosa from ulcerative colitis patients

Cited by 47 publications

References 37 publications

Expression of the REG IV gene in ulcerative colitis

Expression of the REG IV gene in ulcerative colitis

Ulcerative Proctitis, Rectal Prolapse, and Intestinal Pseudo-Obstruction in Transgenic Mice Overexpressing Hepatocyte Growth Factor/Scatter Factor

Amphiregulin and epiregulin expression in neoplastic and inflammatory lesions in the colon

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