Reg protein is a unique growth factor of gastric mucosal cells

Kinoshita, Yoshikazu; Ishihara, Shunji; Kadowaki, Yasunori; Fukui, Hiroshi; Chiba, Tsutomu

doi:10.1007/s00535-004-1354-5

Cited by 56 publications

(43 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reg I is an acinar cell-derived product of the pancreas, is constitutively expressed and secreted from the acinar cells, and can be ectopically induced within regenerating islets. Reg I protein is an established mitogen to pancreatic β-, ductal and mucosal cells of the GI tract including the stomach and colon (2,(4)(5). We have shown that purified recombinant reg I is bioactive as well (6), and is mitogenic to primary cultures of ductal cells (6).…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Reg I Binds MKP-1 and Regulates Cyclin D in Pancreatic-Derived Cells

Mueller

Zhang

Zenilman

2008

Journal of Surgical Research

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Pancreatic Reg I Binds MKP-1 and Regulates Cyclin D in Pancreatic-Derived Cells

Mueller

Zhang

Zenilman

2008

Journal of Surgical Research

View full text Add to dashboard Cite

show abstract

“…Recently, many Reg-related genes have been isolated and shown to constitute a multigene family (types I-IV) (8). We have previously reported that REG I␣ and REG IV are involved in the pathophysiology of GI inflammation (5,17) and that, moreover, they act as trophic and/or antiapoptotic factors under inflammatory conditions (17,18).…”

mentioning

confidence: 99%

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Sun

Fukui

Hara

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

Regenerating gene (Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.Reg; nonsteroidal anti-inflammatory drug; proliferation; apoptosis; gastrointestinal mucosa NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) are commonly prescribed worldwide for patients with arthritis or cardiac and cerebrovascular diseases (16). Upper gastrointestinal (GI) damage is a major adverse effect of NSAID use (16), and, moreover, recent evidence suggests that NSAIDs are responsible for mucosal injury, not only in the upper, but also the lower GI tract (10, 16). Prostaglandin synthesis is considered to play a pivotal role in the mechanism of NSAID-induced GI damage (21); however, its pathophysiology still remains to be elucidated.The regenerating gene (Reg) was originally isolated from rat regenerating pancreatic islet cells, and its human homolog was named REG I␣ (23). Recently, many Reg-related genes have been isolated and shown to constitute a multigene family (types I-IV) (8). We have previously reported that REG I␣ and REG IV are involved in the pathophysiology of GI inflammation (5, 17) and that, moreover, they act as trophic and/or antiapoptotic factors under inflammatory conditions (17, 18). Other investigators have reported that Reg III family genes are overexpressed in inflamed GI mucosa (11,13) and that their products, including REG I␣ and REG IV proteins, may exert trophic and/or antiapoptotic effects on panc...

show abstract

“…2,3 Recently, many Reg-related genes have been isolated and shown to constitute a multigene family. 4 Among human REG family proteins, REG Ia and REG IV are reportedly overexpressed in a subset of gastric cancer. [5][6][7][8][9] Moreover, several microarray analyses have recently isolated REG Ia and REG IV as novel genes that are overexpressed in gastric cancer tissues, 10,11 suggesting that both genes have important functions in gastric carcinogenesis.…”

mentioning

confidence: 99%

Expression profile of REG family proteins REG Iα and REG IV in advanced gastric cancer: comparison with mucin phenotype and prognostic markers

et al. 2009

Self Cite

View full text Add to dashboard Cite

Regenerating gene family members 1 (REG Ia) and 4 (REG IV) are overexpressed in a subset of gastric cancers. However, comparative characterization of the expression of these family proteins has remained unclear. Therefore, we aimed to elucidate not only the association between REG protein expression and mucin phenotype but also their significance as a prognostic marker for patients with gastric cancer. The expression of REG Ia, REG IV, CDX2, MUC2, and MUC5AC in gastric cancer tissues was examined by immunohistochemistry. The relationship between REG protein expression and clinicopathological parameters or mucin phenotype was then analyzed. REG Ia and REG IV expression was positive in 33 (52%) and 31 (49%) of 63 gastric cancers examined, respectively. REG Ia expression was significantly related to venous invasion and tumor stage, whereas REG IV expression showed no relationship to clinicopathological features. With regard to mucin phenotype, REG IV expression was significantly correlated with MUC2 and CDX2 expression, suggesting an association with the intestinal mucin phenotype of gastric cancer. On the other hand, REG Ia expression had no correlation with MUC2, CDX2, or MUC5AC in gastric cancer tissues. Expression of REG Ia but not REG IV was an independent predictor of poor outcome in patients with gastric cancer. In addition, patients with gastric cancer negative for both REG Ia and REG IV expression had a significantly better outcome than patients positive for either REG Ia or REG IV. Profiling of REG protein expression is useful to for prognostication of patients with gastric cancer. Modern Pathology ( The regenerating gene (Reg) was originally isolated from regenerating rat pancreatic islets, 1 and its gene product was shown to have a trophic effect on not only islet but also gastric epithelial cells. 2,3 Recently, many Reg-related genes have been isolated and shown to constitute a multigene family. 4 Among human REG family proteins, REG Ia and REG IV are reportedly overexpressed in a subset of gastric cancer. 5-9 Moreover, several microarray analyses have recently isolated REG Ia and REG IV as novel genes that are overexpressed in gastric cancer tissues, 10,11 suggesting that both genes have important functions in gastric carcinogenesis. Indeed, we have previously clarified that REG Ia acts as a trophic and/or anti-apoptotic factor in the development of gastric cancer, 12 and others have reported that REG IV protein confers cell resistance to chemotherapeutic agents, 9 suggesting that these proteins are both associated with tumor progression. It is noteworthy that in non-neoplastic tissues REG Ia and REG IV are commonly expressed not only in endocrine cells but also in metaplastic cells that frequently accompany gastric cancer lesions, 5,8,12,13 implying a possible link between REG protein expression and mucin phenotype of gastric lesions. In addition, there is increasing speculation as to whether REG Ia and REG IV protein expression may

show abstract

Reg protein is a unique growth factor of gastric mucosal cells

Cited by 56 publications

References 32 publications

Pancreatic Reg I Binds MKP-1 and Regulates Cyclin D in Pancreatic-Derived Cells

Pancreatic Reg I Binds MKP-1 and Regulates Cyclin D in Pancreatic-Derived Cells

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Expression profile of REG family proteins REG Iα and REG IV in advanced gastric cancer: comparison with mucin phenotype and prognostic markers

Contact Info

Product

Resources

About