Coordinate Regulation of Secretory Stress Proteins (PSP/reg, PAP I, PAP II, and PAP III) in the Rat Exocrine Pancreas during Experimental Acute Pancreatitis

Graf, Rolf; Schiesser, Marc; Lussi, Adrian; Went, Ph.; Scheele, George A.; Bimmler, Daniel

doi:10.1006/jsre.2002.6387

Cited by 92 publications

(98 citation statements)

References 19 publications

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“…The substantial induction of PAP-III in injured peripheral nerves is quite a specific response that has not been observed in other tissue injury models (data not shown), although acute pancreatitis can induce PAP-III mRNA expression together with the mRNAs of other Reg/PAP family members (Dusetti et al, 1995;Graf et al, 2002). In particular, we did not detect any induction of PAP-III expression in CNS glial cells, such as oligodendrocytes, or astrocytes in our spinal cord injury model .…”

Section: Discussioncontrasting

confidence: 44%

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

et al. 2006

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Circulating macrophages are recruited to degenerating nerves in response to nerve injury to remove myelin and axonal debris, a process that is crucial for successful nerve regeneration. In this study, we demonstrate that pancreatitis-associated protein (PAP)-III is a macrophage chemoattractant that is induced in and released from injured nerves. In vitro experiments revealed that PAP-III possessed a strong macrophage chemoattractant activity that was comparable with that of monocyte chemoattractant protein-1. In addition, gene knockdown via adenovirus-mediated small interference RNA expression in isolated sciatic nerves successfully suppressed PAP-III expression and its macrophage chemoattractant activity. Furthermore, overexpression or knockdown of the PAP-III gene in crushed sciatic nerves in rats resulted in acceleration or retardation of macrophage recruitment and subsequent nerve regeneration, respectively. Collectively, our results demonstrate that PAP-III is a novel macrophage chemoattractant that is involved in peripheral nerve regeneration and further provide new insights into Schwann cell-macrophage interactions and therapeutic interventions.

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Section: Discussioncontrasting

confidence: 44%

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

et al. 2006

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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: 93%

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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“…It is also induced in regenerating islets (Terazono et al, 1988) (hence, the name Reg), and it can ameliorate surgical diabetes (Okamoto, 1999). Reg-I is upregulated during rat pancreatitis, although the extent of induction varies among different studies (Zenilman et al, 2000;Graf et al, 2002). With regard to other Regs, members Mice were euthanized at the indicated times after the beginning of CDD feeding, followed by analysis of total pancreas homogenates by immunoblotting using antibodies to the indicated proteins.…”

Section: The Reg Family Members and Response To Injurymentioning

confidence: 99%

“…18, December 2007of the Reg-III subfamily are also up-regulated during mouse pancreatitis, and the use of antisense oligonucleotides directed toward Reg-III exacerbates the severity of rat pancreatitis (Zenilman et al, 2000;Graf et al, 2002;Zhang et al, 2004;Norkina et al, 2006).…”

Section: Regulation Of Reg-ii By Keratinsmentioning

confidence: 99%

“…We tested this hypothesis by using an unbiased expression profiling approach, and we noted marked up-regulation of several regenerating isletderived (Reg) family members. The Reg proteins are established stress-inducible proteins that ameliorate pancreatic injury (Graf et al, 2002;Bimmler et al, 2004;Zhang et al, 2004) and may therefore functionally compensate for the lack of keratins in the pancreas. We also examined changes in Reg expression in keratin mouse models that have altered keratin filament organization or phosphorylation.…”

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confidence: 99%

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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

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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...

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Coordinate Regulation of Secretory Stress Proteins (PSP/reg, PAP I, PAP II, and PAP III) in the Rat Exocrine Pancreas during Experimental Acute Pancreatitis

Cited by 92 publications

References 19 publications

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

Expression of the REG IV gene in ulcerative colitis

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

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