Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease

Gironella, Meritxell

doi:10.1136/gut.2004.056309

Cited by 94 publications

(108 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 Exprementioning

confidence: 76%

Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

View full text Add to dashboard Cite

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...

show abstract

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

confidence: 76%

Expression of the REG IV gene in ulcerative colitis

Nanakin

Fukui

Fujii

et al. 2007

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…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%

“…14 Higher levels of Reg3a were documented in patients with IBD in comparison to healthy controls, while no significant increase was seen in patients with infectious colitis. 8,17 Reg3a is also increased in the plasma of patients with gastrointestinal GVHD, and this protein has been proposed as a useful biomarker that may improve risk stratification of GVHD patients when combined with clinical stage and histological grading. 19 Our study was performed to evaluate whether serum Reg3a concentration is increased in patients with mucosal enteropathies.…”

mentioning

confidence: 99%

“…22 Analysis of Reg3a in human IBD has revealed that the protein is up-regulated in inflamed gut of patients with Crohn's disease and UC, and in vitro treatment of IBD mucosal biopsies with exogenous Reg3a is associated with a marked inhibition of immune-inflammatory pathways, 17 thus highlighting the possibility that Reg proteins can counteract detrimental reactions in the gut. Serum/plasma concentration of Reg proteins can increase during various inflammatory conditions.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Serum regenerating islet‐derived 3‐alpha is a biomarker of mucosal enteropathies

Marafini

Sabatino

Zorzi

et al. 2014

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…The mechanism for a potential Reg-II-mediated protective effect remains to be defined, because there is no clearly established Reg-II function. By analogy with other Regs, Reg-II may function at one or more levels by enhancing the regenerative capacity (Okamoto, 1999;Patard et al, 2003); or by imparting anti-inflammatory, antiapoptotic, and/or mitogenic effects (Malka et al, 2000;Vasseur et al, 2004;Gironella et al, 2005). It will be important to address whether the effect of Reg-II is paracrine, endocrine, or autocrine.…”

Section: Reg-ii As a Potential Compensatory Pancreatic Stress Proteinmentioning

confidence: 99%

Reg-II Is an Exocrine Pancreas Injury-Response Product That Is Up-Regulated by Keratin Absence or Mutation

Zhong

Strnad

Toivola

et al. 2007

MBoC

View full text Add to dashboard Cite

The major keratins in the pancreas and liver are keratins 8 and 18 (K8/K18), but their function seemingly differs in that liver K8/K18 are essential cytoprotective proteins, whereas pancreatic K8/K18 are dispensable. This functional dichotomy raises the hypothesis that K8-null pancreata may undergo compensatory cytoprotective gene expression. We tested this hypothesis by comparing the gene expression profile in pancreata of wild-type and K8-null mice. Most prominent among the up-regulated genes in K8-null pancreas was mRNA for regenerating islet-derived (Reg)-II, which was confirmed by quantitative reverse transcription-polymerase chain reaction and by an anti-Reg-II peptide antibody we generated. Both K8-null and wild-type mice express Reg-II predominantly in acinar cells as determined by in situ hybridization and immunostaining. Analysis of Reg-II expression in various keratin-related transgenic mouse models showed that its induction also occurs in response to keratin cytoplasmic filament collapse, absence, or ablation of K18 Ser52 but not Ser33 phosphorylation via Ser-to-Ala mutation, which represent situations associated with predisposition to liver but not pancreatic injury. In wild-type mice, Reg-II is markedly up-regulated in two established pancreatitis models in response to injury and during the recovery phase. Thus, Reg-II is a likely mouse exocrine pancreas cytoprotective candidate protein whose expression is regulated by keratin filament organization and phosphorylation. INTRODUCTIONIntermediate filaments (IFs), microfilaments, and microtubules are the three major cytoskeletal protein groups of mammalian cells (Bershadsky and Vasiliev, 1988;Ku et al., 1999). All IFs share a common prototype structure consisting of a coiled-coil ␣-helical rod domain that is interrupted by linkers and flanked by non-␣-helical N-terminal "head" and C-terminal "tail" domains (Fuchs and Cleveland, 1998;Herrmann et al., 2003;Coulombe and Wong, 2004;Herrmann and Aebi, 2004). Within the IF family, keratins are the largest subfamily, and they make up the IFs of epithelial cells, whereas other IFs are characteristic of unique cell types (e.g., desmin in myocytes, neurofilaments in neuronal cells). This tissue-specific expression reflects the involvement of IFs in a broad range of tissue-selective human diseases (Fuchs and Cleveland, 1998;Omary et al., 2004). Keratins (K) include the type I and type II IFs, and all epithelial cells express at least one type I and one type II keratins as obligate noncovalent heteropolymers (Moll et al., 1982;Schweizer et al., 2006). In simple-type epithelia, as found in the liver, pancreas, and intestine, the major keratins are K18/K19/K20 (type I) and K7/K8 (type II), with the K8/K18 pair being dominant depending on the tissue (Moll et al., 1982;Ku et al., 1999;Herrmann et al., 2003;Zhou et al., 2003).Keratin networks are versatile structures that undergo dynamic reorganization in response to a variety of intra-and extracellular cues. Posttranslational modifications and keratin-binding partners...

show abstract

Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease

Cited by 94 publications

References 40 publications

Expression of the REG IV gene in ulcerative colitis

Expression of the REG IV gene in ulcerative colitis

Serum regenerating islet‐derived 3‐alpha is a biomarker of mucosal enteropathies

Reg-II Is an Exocrine Pancreas Injury-Response Product That Is Up-Regulated by Keratin Absence or Mutation

Contact Info

Product

Resources

About