Identification of a novel Reg family gene, Reg IIIδ, and mapping of all three types of Reg family gene in a 75 kilobase mouse genomic region

Abe, Michiaki; Nata, Koji; Akiyama, Takako; Shervani, Nausheen J.; Kobayashi, Seiichi; Tomioka-Kumagai, Tomoko; Ito, Sadayoshi; Takasawa, Shin; Okamoto, Hiroshi

doi:10.1016/s0378-1119(00)00059-7

Cited by 69 publications

(67 citation statements)

References 28 publications

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“…However, no definitive post-translational modification could be derived from our mass spectrometry data. The mouse Reg genes are located in a contiguous region in chromosome 6 (37). The mouse has two Reg genes, Reg1 and Reg2, with the mouse Reg1 gene having slightly higher homology to the rat and human REG1 gene than Reg2 (38).…”

Section: /11mentioning

confidence: 99%

Differentially Expressed Proteins in the Pancreas of Diet-induced Diabetic Mice

Qiu

List

Kopchick

2005

Molecular & Cellular Proteomics

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The pancreas is a heterogeneous organ mixed with both exocrine and endocrine cells. The pancreas is involved in metabolic activities with the endocrine cells participating in the regulation of blood glucose, while the exocrine portion provides a compatible environment for the pancreatic islets and is responsible for secretion of digestive enzymes. The purpose of this study was to identify pancreatic proteins that are differentially expressed in normal mice and those with diet-induced type 2 diabetes (T2DM). In this study, C57BL/6J male mice fed a high fat diet became obese and developed T2DM. The pancreatic protein profiles were compared between control and diabetic mice using two-dimensional gel electrophoresis. Differentially expressed protein "spots" were identified by mass spectrometry. REG1 and REG2 proteins, which may be involved in the proliferation of pancreatic beta cells, were up-regulated very early in the progression of obese mice to T2DM. Glutathione peroxidase, which functions in the clearance of reactive oxidative species, was found to be down-regulated in the diabetic mice at later stages. The RNA levels encoding REG2 and glutathione peroxidase were compared by Northern blot analysis and were consistent to the changes in protein levels between diabetic and control mice. The up-regulation of REG1 and REG2 suggests the effort of the pancreas in trying to ameliorate the hyperglycemic condition by stimulating the proliferation of pancreatic beta cells and enhancing the subsequent insulin secretion. The down-regulation of glutathione peroxidase in pancreas could contribute to the progressive deterioration of beta cell function due to the hyperglycemia-induced oxidative stress. Molecular & Cellular Proteomics 4:1311-1318, 2005.

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Section: /11mentioning

confidence: 99%

Differentially Expressed Proteins in the Pancreas of Diet-induced Diabetic Mice

Qiu

List

Kopchick

2005

Molecular & Cellular Proteomics

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“…[7][8][9][10] The Reg family genes included six members (Reg I, Reg II, Reg IIIa, Reg IIIb, Reg IIId and Reg IIIg) in the mouse and three members (Reg Ia, Reg Ib and Reg III) in humans. 11 Human Reg IV, a novel member of the family was identified by high throughput sequencing of a library derived from patients with ulcerative colitis, constituting fourth member of the Reg gene family in human. 10 A mouse homologue has also been identified constituting the seventh member in mouse.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes

Bishnupuri

Luo

Korzenik

et al. 2006

Cancer Biology & Therapy

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Expression of anti-apoptotic genes is frequently elevated in tumors, where they increase resistance to chemotherapeutic agents and predict poor patient outcomes. However, key cellular factors regulating anti-apoptotic genes in tumors remain unknown. Increased expression of the regenerating (Reg) genes is commonly observed in gastrointestinal (GI) malignancies including colorectal cancer (CRC). We therefore examined Reg gene expression and associated changes in anti-apoptotic genes in an animal model of GI tumorigenesis. Using real time RT-PCR, we measured expression of Reg genes in human colorectal adenocarcinoma specimens, colon adenocarcinoma cell lines and adenomas from multiple intestinal neoplasia (min) mice heterozygous for a germ-line mutation of the adenomatous polyposis coli (APC) gene. Expression of Reg genes is increased in human colorectal adenocarcinomas and in the intestine of APC min/+ mice at four weeks of age, a time preceding the spontaneous second mutation in the APC gene. Individual Reg genes exhibited regional expression profiles across the GI tract in mice. Adenomas from 14-week old mice had significant increases in at least one member of the Reg gene family, most commonly Reg IV and an associated increase in expression of the anti-apoptotic gene, Bcl-2. Addition of exogenous recombinant human Reg IV to human colon adenocarcinoma cells significantly increased Bcl-2 and Bcl-x L expression and induced resistance to ionizing radiation. These results show that dysregulation of Reg genes occur early in tumorigenesis. Furthermore, increased expression of Reg genes, specifically Reg IV contribute to adenoma formation and lead to increased resistance to apoptotic cell death in CRC.

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“…This result is not unexpected, given the presence of IL-6 responsive elements in the promoters of several Reg and HIP/PAP genes (Dusetti et al 1995, Abe et al 2000, Nata et al 2004. Interestingly, IL-6 has been reported to stimulate expression of human HIP/PAP gene (Gurr et al 2002), but had no effect on expression of rat PAP1 and Reg1 genes when administered alone (Dusetti et al 1996, Akiyama et al 2001.…”

Section: Effect Of Cytokines and Gf On Ingap Expressionmentioning

confidence: 76%

Development of an in vitro pancreatic tissue model to study regulation of islet neogenesis associated protein expression

Petropavlovskaia

Makhlin²,

Sampalis

et al. 2006

Journal of Endocrinology

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Restoration of a functional b-cell mass in a patient with diabetes may hold the key for curing the disease. In recent years, there has been increasing interest in the development of new strategies to induce b-cell regeneration and new islet formation in situ and a role for Reg proteins has been suggested. One such protein, islet neogenesis associated protein (INGAP), is a member of the Reg3 family of proteins and has been shown to induce islet neogenesis. Elucidation of the mechanisms and factors involved in the regulation of expression of INGAP and related proteins is, therefore, of great importance. Here, we report the establishment of the first in vitro tissue model of INGAP expression that consists of epithelial cystic structures derived from hamster pancreatic acinar tissue cultured in collagen matrix. The objective of this study was to characterize INGAP expression in this model and to investigate the role of pro-inflammatory cytokines and growth factors. Using quantitative reverse transcriptase PCR, we show that INGAP expression correlates with cyst formation and size suggesting the involvement of intra-luminal pressure associated with cyst growth. We also demonstrate for the first time that INGAP gene expression was significantly induced by treatment with interleukin (IL)-6 and further enhanced by a combination of IL-6 with dexamethazone and nicotinamide. Additionally, our data suggest that the effect of IL-6 on INGAP expression is mediated via the JAK/STAT3 signaling pathway. In summary, the in vitro model of INGAP expression described here represents an important step in the development of strategies for the use of INGAP and related proteins as islet neogenic agents in the pharmacotherapy of both type-1 and type-2 diabetes.

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Identification of a novel Reg family gene, Reg IIIδ, and mapping of all three types of Reg family gene in a 75 kilobase mouse genomic region

Cited by 69 publications

References 28 publications

Differentially Expressed Proteins in the Pancreas of Diet-induced Diabetic Mice

Differentially Expressed Proteins in the Pancreas of Diet-induced Diabetic Mice

Dysregulation of reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes

Development of an in vitro pancreatic tissue model to study regulation of islet neogenesis associated protein expression

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