Effects of Helicobacter pylori Infection on the Link between Regenerating Gene Expression and Serum Gastrin Levels in Mongolian Gerbils

Fukui, Hirokazu; Franceschi, Francesco; Penland, Rebecca L.; Sakai, Tomoya; Sepulveda, Antonia R.; Fujimori, Takahiro; Terano, Akira; Chiba, Tsutomu; Genta, Robert M.

doi:10.1097/01.lab.0000106501.56339.ce

Cited by 50 publications

(31 citation statements)

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“…Although the aetiology of SS is still unclear, it is thought to be an autoimmune disease characterized by marked ductal cell destruction with inflammatory cell infiltration in MSG [40]. It was reported previously that REG Iα is expressed not only in various human inflammatory diseases such as gastritis [41], pancreatitis [42] and colitis, but also in various experimental models of inflammation in animal tissues [39,43]. Thus, it is most likely that inflammation, regardless of whether or not it is autoimmune-associated, is a key event triggering REG Iα expression in many tissues.…”

Section: Discussionmentioning

confidence: 99%

Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome

Yoshimoto

Fujimoto

Itaya‐Hironaka

et al. 2013

Clinical and Experimental Immunology

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SummaryThe regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcriptionpolymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibodynegative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by RubinHolt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.

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Section: Discussionmentioning

confidence: 99%

Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome

Yoshimoto

Fujimoto

Itaya‐Hironaka

et al. 2013

Clinical and Experimental Immunology

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“…In previous studies, we and others have demonstrated that the REG Ia gene is involved in inflammatory diseases 27,28 and that its expression is enhanced by proinflammatory cytokines such as IFN-g and IL-6. 9,12,[29][30][31] On the other hand, others have also demonstrated enhancement of REG III gene expression by several cytokines.…”

Section: Effects Of Reg IVmentioning

confidence: 99%

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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“…Both apoptosis and cell proliferation are increased in precancer lesions (atrophy, metaplasia, dysplasia) in the presence of H. pylori infection (59). A disregulation of genes controlling apoptosis and hence homeostasis between apoptosis and cell proliferation may ultimately lead to tumor development (60).…”

Section: A Link Between H Pylori Apoptosis and Cell Proliferationmentioning

confidence: 99%