Increased Expression of HIP/PAP and Regenerating Gene III in Human Inflammatory Bowel Disease and a Murine Bacterial Reconstitution Model

Ogawa, Hitoshi; Fukushima, Kouhei; Naitö, Hiroo; Funayama, Yuji; Unno, Michiaki; Takahashi, Ken; Kitayama, Taku; Matsuno, Seiki; Ohtani, Hideyuki; Takasawa, Shin; Okamoto, Hiroshi; Sasaki, Iwao

doi:10.1097/00054725-200305000-00003

Cited by 149 publications

(139 citation statements)

References 37 publications

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“…12 Moreover, others have reported an increase of REG III gene expression in UC mucosa. 21,22 Thus, our present study showing that the REG IV gene is also upregulated in the UC colonic mucosa strongly suggests generalized upregulation of REG family genes in the colonic mucosa of UC patients.…”

Section: Effects Of Cytokines and Growth Factors On Reg IV Gene Expresupporting

confidence: 64%

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 Cytokines and Growth Factors On Reg IV Gene Expresupporting

confidence: 64%

Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

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“…These results suggest that C-mix may inhibit the expression of these infl ammatory cytokines and chemokines by the regulation of CCL4 expression. Overexpression of pancreatitis-associated protein (Pap) was detected in the colonic mucosa of IBD patients and DSSinduced colitic mice (Ogawa et al, 2003). Additionally, gene members of the S-100 calcium binding protein family, endogenous activators of innate immune responses, overexpressed in IBD patients were increased, like the previously reports (Lawrance et al, 2001;Dieckgraefe et al, 2002;te Velde et al, 2007).…”

supporting

confidence: 70%

Evaluation of Anti-Colitic Effect of Chung-Jang-Hwan (C-mix) in Mice

Lee¹,

Ahn²,

Park³

et al. 2011

Biomolecules and Therapeutics

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The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of infl ammation-related genes, including IL-1β, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of infl ammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-1β, representative infl ammatory genes, were confi rmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of infl ammation-associated genes. 52-58 (2011) www.biomolther.org Abstract

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“…14 Similarly, Reg3a, also termed pancreatitis associated protein, is over-expressed in colonic tissue of IBD patients, and the serum levels of this protein are increased in patients with either clinically active or inactive IBD patients as compared to normal controls. [15][16][17] Analysis of cell source of Reg proteins in the human gut revealed that metaplastic Paneth cells in both un-inflamed samples from IBD patients and in inflamed colonic mucosa express Reg1a, Reg1b and Reg3a mRNA. 18 Elevated levels of Reg3a have also been documented in plasma samples of patients with gastrointestinal graft-versus host disease (GVHD), and the concentrations of this biomarker at onset of GVHD seem to predict response to treatment and correlate with severity of mucosal denudation.…”

Section: Introductionmentioning

confidence: 99%