Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly

BACKGROUND Regenerating gene 4(REG4)has been proved to be carcinogenic in some cancers,but its manifestation and possible carcinogenic mechanisms in colorectal cancer(CRC)have not yet been elucidated.Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism.AIM To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance.METHODS We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC.The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells.We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells.Finally,we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells.RESULTS Compared to normal mucosa,REG4 mRNA expression was high in CRC(P<0.05)but protein expression was low.An inverse correlation existed between lymph node and distant metastases,tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression(P<0.05),but vice versa for REG4 protein expression.REG4-related genes included:Chemokine activity;taste receptors;protein-DNA and DNA packing complexes;nucleosomes and chromatin;generation of second messenger molecules;programmed cell death signals;epigenetic regulation and DNA methylation;transcription repression and activation by DNA binding;insulin signaling pathway;sugar metabolism and transfer;and neurotransmitter receptors(P<0.05).REG4 exposure or overexpression promoted proliferation,antiapoptosis,migration,and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway.REG4 was involved in chemoresistance not through de novo lipogenesis,but lipid droplet assembly.REG4 inhibited the transcription of acetyl-CoA carboxylase 1(ACC1)and ATP-citrate lyase(ACLY)by disassociating the complex formation of anti-acetyl(AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY.CONCLUSION REG4 may be involved in chemoresistance through lipid droplet assembly.REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.

Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration

AIM: To study the action of the genes associated with drug-induced liver diseases at the gene transcriptional level during liver regeneration (LR) in rats. METHODS: The genes associated with drug-induced liver diseases were obtained by collecting the data from databases and literature, and the gene expression changes in the regenerating liver were checked by the Rat Genome 230 2.0 array. RESULTS: The initial and total expression numbers of genes occurring in phases of 0.5-4 h after partial hepatectomy (PH), 4-6 h after PH (G0/G1 transition), 6-66 h after PH (cell proliferation), 66-168 h after PH (cell differentiation and structure-function reconstruction) were 21, 3, 9, 2 and 21, 9, 19, 18, respectively. It is illustrated that the associated genes were mainly triggered at the initial stage of LR and worked at different phases. According to their expression similarity, these genes were classified into 5 types: only up- regulated (12 genes), predominantly up-regulated (4 genes), only down-regulated (11 genes), predominantly down-regulated (3 genes), and approximately up-/ down-regulated (2 genes). The total times of their up- and down-expression were 130 and 79, respectively, demonstrating that expression of most of the genes was increased during LR, while a few decreased. The cell physiological and biochemical activities during LR were staggered according to the time relevance and were diverse and complicated in gene expression patterns. CONCLUSION: Drug metabolic capacity in regenerating liver was enhanced. Thirty-two genes play important roles during liver regeneration in rats.

Expression patterns and action analysis of genes associated with inflammatory responses during rat liver regeneration

AIM： To study the relationship between inflammatory response and liver regeneration （LR） at transcriptional level.METHODS： After partial hepatectomy （PH） of rats, the genes associated with inflammatory response were obtained according to the databases, and the gene expression changes during LR were checked by the Rat Genome 230 2.0 army. RESULTS： Two hundred and thirty-nine genes were associated with liver regeneration. The initial and total expressing gene numbers found in initiation phase （0.5-4 h after PH）, G0/G1 transition （4-6 h after PH）, cell proliferation （6-66 h after PH）, cell differentiation and structure-function reconstruction （66-168 h after PH） of liver regeneration were 107, 34, 126, 6 and 107, 92, 233, 145 respectively, showing that the associated genes were mainly triggered at the beginning of liver regeneration, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups： only up-regulated, predominantly up-, only down-, predominantly down-, up- and down-, involving 92, 25, 77, 14 and 31 genes, respectively. The total times of their up- and down-regulated expression were 975 and 494, respectively, demonstrating that the expressions of the majority of genes were increased, and that of a few genes were decreased. Their time relevance was classified into 13 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 33 types, suggesting that the activities were diverse and complex during liver regeneration. CONCLUSION： Inflammatory response is closelyassociated with liver regeneration, in which 239 LR- associated genes play an important role.

Expression patterns and action analysis of genes associated with blood coagulation responses during rat liver regeneration

AIM: To study the blood coagulation response after partial hepatectomy (PH) at transcriptional level. METHODS: After PH of rats, the associated genes with blood coagulation were obtained through reference to the databases, and the gene expression changes in rat regenerating liver were analyzed by the Rat Genome 230 2.0 array. RESULTS: It was found that 107 genes were associated with liver regeneration. The initially and totally expressing gene numbers occurring in initiation phase of liver regeneration (0.5-4 h after PH), G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) were 44, 11, 58, 7 and 44, 33, 100, 71 respectively, showing that the associated genes were mainly triggered in the forepart and prophase, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups: only up-, predominantly up-, only down-, predominantly down-, up- and down-regulation, involving 44, 8, 36, 13 and 6 genes, respectively, and the total times of their up- and down-regulation expression were 342 and 253, respectively, demonstrating that the number of the up-regulated genes was more than that of the down- regulated genes. Their time relevance was classified into 15 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 29 types, suggesting that their protein activities were diverse and complex during liver regeneration.CONCLUSION: The blood coagulation response is enhanced mainly in the forepart, prophase and anaphase of liver regeneration, in which the response in the forepart, prophase of liver regeneration can prevent the bleeding caused by partial hepatectomy, whereas that in the anaphase contributes to the structure-function reorganization of regenerating liver. In the process, 107 genes associated with liver regeneration play an important role.

Expression patterns and action analysis of genes associated with hepatitis virus infection during rat liver regeneration

AIM： To study the action of hepatitis virus infectionassociated genes at transcription level during liver regeneration （LR）. METHODS： Hepatitis virus infection-associated genes were obtained by collecting the data from databases and retrieving the correlated articles, and their expression changes in the regenerating rat liver were detected with the rat genome 230 2.0 array. RESULTS： Eighty-eight genes were found to be associated with liver regeneration. The number of genes initially and totally expressed during initial LR [0.5-4 h affer partial hepatectomy （PH）], transition from （30 to G1 （4-6 h affer PH）, cell proliferation （6-66 h after PH）, cell differentiation and reorganization of structurefunction （66-168 h after PH） was 37, 8, 48, 3 and 37, 26, 80, 57, respectively, indicating that the genes were mainly triggered at the early stage of LR （0.5-4 h after PH）, and worked at different phases. These genes were classified into 5 types according to their expression similarity, namely 37 up-regulated, 9 predominantly upregulated, 34 down-regulated, 6 predominantly downregulated and 2 up/down-regulated genes. Their total up- and down-regulation frequencies were 359 and 149 during LR, indicating that the expression of most genes was enhanced, while the expression of a small number of genes was attenuated during LR. According to time relevance, they were classified into 12 groups （0.5 and 1h, 2 and 4h, 6h, 8 and 12h, 16 and 96h, 18 and 24 h, 30 and 42 h, 36 and 48 h, 54 and 60 h, 66 and 72 h, 120 and 144 h, 168 h）, demonstrating that the cellular physiological and biochemical activities during LR were fluctuated. According to expression changes of the genes, their expression patterns were classified into 23 types, suggesting that the cellular physiological and biochemical activities during LR were diverse and complicated. CONCLUSION： The anti-virus infection capacity of regenerating liver can be enhanced and 88 genes play an important role in LR.

Gene therapy and the regeneration of retinal ganglion cell axons

Because the adult mammalian central nervous system （CNS） has only limited intrinsic capacity to regenerate connections after injury, due to factors both intrinsic and extrinsic to the mature neuron （Shen et al., 1999; Berry et al., 2008; Lingor et al., 2008; Sun and He, 2010; Moore et al., 2011 ）, therapies are required to support the survival of injured neu-rons and to promote the long-distance regrowth of axons back to their original target structures. The retina and optic nerve （ON） are part of the CNS and this system is much used in experiments designed to test new ways of promoting regeneration after injury （Harvey et al., 2006; Benowitz and Yin, 2008; Berry et al., 2008; Fischer and Leibinger, 2012）. Testing of therapies designed to improve retinal ganglion cell （RGC） viability also has direct clinical relevance because there is loss of these centrally projecting neurons in many ophthalmic diseases.

Role of microRNA in liver regeneration

BACKGROUND： Liver regeneration is a complex process. micro RNAs（mi RNAs） are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that mi RNAs are closely linked to liver regeneration.DATA SOURCES： All included studies were obtained from Pub Med, Embase, the Science Direct databases and Web of Science, with no limitation on publication year. Only studies published in English were considered.RESULTS： We grouped studies that involved mi RNA and liver regeneration into two groups： mi RNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant mi RNAs separately from the related pathways.CONCLUSIONS： Blocking or stimulating the pathways of mi RNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of mi RNA.

Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration:Innate immune response

AIM： To study the relationship between innate immune response and liver regeneration （LR） at transcriptional level.METHODS： Genes associated with innate immunity response were obtained by collecting the data from databases and retrieving articles, Gene expression changes in rat regenerating liver were detected by rat genome 230 2.0 array.RESULTS： A total of 85 genes were found to be associated with LR. The initially and totally expressed number of genes at the phases of initiation [0.5-4 h after partial hepatectomy （PH）], transition from GO to G1 （4-6 h after PH）, cell proliferation （6-66 h after PH）, cell differentiation and structure-function reconstruction （66-168 h after PH） was 36, 9, 47, 4 and 36, 26, 78, 50, respectively, illustrating that the associated genes were mainly triggered at the initial phase of LR and worked at different phases. According to their expression similarity, these genes were classified into 5 types： 41 up-regulated, 4 predominantly up-regulated, 26 downregulated, 6 predominantly down-regulated, and 8 approximately up/down-regulated genes, respectively. The expression of these genes was up-regulated 350 times and down-regulated 129 times respectively, demonstrating that the expression of most genes was enhanced while the expression of a small number of genes was decreased during LR. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities dudng LR were staggered. According to the gene expression patterns,they were classified into 28 types, indicating that the cellular physiological and biochemical activities were diverse and complicated during LR. CONCLUSION： Congenital cellular immunity is enhanced mainly in the forepart, prophase and anaphase of LR while congenital molecular immunity is increased dominantly in the forepart and anaphase of LR. A total of 85 genes associated with LR play an important role in innate immunity.

Expression pattern and action analysis of genes associated with the responses to chemical stimuli during rat liver regeneration

AIM: To study the genes associated with the responses to chemokines, nutrients, inorganic substances, organic substances and xenobiotics after rat partial hepatectomy (PH) at transcriptional level. METHODS: The associated genes involved in the five kinds of responses were obtained from database and literature, and the gene expression changes during liver regeneration in rats were checked by the Rat Genome 230 2.0 array. RESULTS: It was found that 60, 10, 9, 6, 26 genes respectively participating in the above five kinds of responses were associated with liver regeneration. The numbers of initially and totally expressed genes occurring in the initial phase of liver regeneration (0.5-4 h after PH), G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure- functional reconstruction (66-168 h after PH) were 51, 19, 52, 6 and 51, 43, 98, 68 respectively, illustrating that the associated genes were mainly triggered in the initiation and transition stages, and functioned at different phases. According to their expression similarity, these genes were classified into 5 groups: only up- regulated (47), predominantly up-regulated (18), only down-regulated (24), predominantly down-regulated (10), and up- and down-regulated (8). The total times of their up-regulated and down-regulated expression were 441 and 221, demonstrating that the number of up- regulated genes is more than that of the down-regulated genes. Their time relevance and gene expression patterns were classifi ed into 14 and 26 groups, showing that the cell physiological and biochemical activitieswere staggered, diversifi ed and complicated during liver regeneration in rats. CONCLUSION: The chemotaxis was enhanced mainly in the forepart and metaphase of LR. The response of regenerating liver to nutrients and chemical substances was increased, whereas that to xenobiotics was not strong. One hundred and seven genes associated with LR play important roles in the responses to chemical substances.

Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration

Each neuronal subtype is distinct in how it develops,responds to environmental cues,and whether it is capable of mounting a regenerative response following injury.Although the adult central nervous system（CNS） does not regenerate,several experimental interventions have been trialled with successful albeit limited instances of axonal repair.We highlight here some of these approaches including extracellular matrix（ECM） modification,cellular grafting,gene therapy-induced replacement of proteins,as well as application of biomaterials.We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons.More specifically,we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts,whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons.Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration.We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.

Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration:Cellular immune response

AIM： To study the cellular immune response during rat liver regeneration （LR） at a transcriptional level. METHODS： Genes associated with the cellular immune response were obtained by collecting the data from databases and retrieving articles. Gene expression changes during LR were detected by rat genome 230 2.0 array. RESULTS： A total of 127 genes were found to be associated with LR. The number of initially and totally expressing genes in the initial phase of LR [0.5-4 h after partial hepatectomy （PH）], transition from Go-G, （4-6 h after PH）, cell proliferation （6-66 h after PH）, cell differentiation and structure-function reconstruction （66-168 h after PH） was 54, 11, 34, 3 and 54, 49, 70, 49 respectively, illustrating that the associated genes were mainly triggered at the initiation of LR, and worked at different phases. According to their expression similarity, these genes were classified into 41 up-regulated, 21 predominantly up-regulated, 41 down-regulated, 14 predominantly down-regulated, 10 similarly up-regulated and down-regulated genes, respectively. The total up- and down-regulated expression times were 419 and 274, respectively, demonstrating that the expression of most genes was increased while the expression of a small number of genes was decreased. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities were staggered during LR. According to the gene expression patterns, they were classified into 21 types, showing the activities were diverse and complicated during LR.CONCLUSION： Antigen processing and presentation are enhanced mainly in the forepart, prophase and anaphase of LR. T-cell activation and antigen elimination are enhanced mainly in the forepart and prophase of LR. A total of 127 genes associated with LR play an important role in cellular immunity.

Beta-nerve growth factor promotes neurogenesis and angiogenesis during the repair of bone defects

We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor（β-NGF） on neurogenesis and angiogenesis in critical-sized bone defects filled with collagen bone substitute. We created two symmetrical defects, 2.5 mm in diameter, on either side of the parietal bone of the skull, and filled them with bone substitute. Subcutaneously implanted osmotic pumps were used to infuse 10 μgβ-NGF in PBS（β-NGF ＋ PBS） into the right-hand side defect, and PBS into the left（control） defect, over the 7 days following surgery. Immunohistochemical staining and hematoxylin-eosin staining were carried out at 3, 7, 14, 21 and 28 days postoperatively. On day 7, expression of β III-tubulin was lower on the β-NGF ＋ PBS side than on the control side, and that of neurofilament 160 was greater. On day 14, β III-tubulin and protein gene product 9.5 were greater on the β-NGF ＋ PBS side than on the control side. Vascular endothelial growth factor expression was greater on the experimental side than the control side at 7 days, and vascular endothelial growth factor receptor 2 expression was elevated on days 14 and 21, but lower than control levels on day 28. However, no difference in the number of blood vessels was observed between sides. Our results indicate that topical application of β-NGF promoted neurogenesis, and may modulate angiogenesis by promoting nerve regeneration in collagen bone substitute-filled defects.

Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury

The neural regeneration process is driven by a wide range of molecules and pathways. Adherens junctions are critical cellular junctions for the integrity of peripheral nerves. However, few studies have systematically characterized the transcript changes in the adherens junction pathway following injury. In this study, a rat model of sciatic nerve crush injury was established by forceps. Deep sequencing data were analyzed using comprehensive transcriptome analysis at 0, 1, 4, 7, and 14 days after injury. Results showed that most individual molecules in the adherens junctions were either upregulated or downregulated after nerve injury. The m RNA expression of ARPC1 B, ARPC3, TUBA8, TUBA1 C, CTNNA2, ACTN3, MET, HGF, NME1 and ARF6, which are involved in the adherens junction pathway and in remodeling of adherens junctions, was analyzed using quantitative real-time polymerase chain reaction. Most of these genes were upregulated in the sciatic nerve stump following peripheral nerve injury, except for CTNNA2, which was downregulated. Our findings reveal the dynamic changes of key molecules in adherens junctions and in remodeling of adherens junctions. These key genes provide a reference for the selection of clinical therapeutic targets for peripheral nerve injury.

DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms（rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266） in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models（Codominant, Dominant, Recessive, Heterozygote advantage, and Allele） between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs（rs807724, rs2274305, and rs4599626） were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype（rs9295619-rs807701-rs807724-rs2274305） and the T-A of the two-marker haplotype（rs3765502-1087266） were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healingassociated genes

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

Protection of 3'-methoxy-puerarin against focal brain ischemia and its association with c-fos expression

The present study established a rat model of focal brain ischemia by occlusion of the middle cerebral artery covered with FeCl3, and investigated the protective effect of 3＇-methoxy-puerarin. Hippocampal and cortical c-fos gene expression was determined using in situ hybridization. Results showed that 3＇-methoxy-puerarin reduced neurological deficit scores, cerebral infarcted zone and water content of brain tissues, dramatically increased the activity of catalase and glutathione peroxidase in the ischemia zone of the hippocampus, increased the activity of catalase in the cortex, decreased lipid peroxide and lactic acid contents in the hippocampus and cerebral cortex, and down-regulated c-fos gene expression in brain ischemic rats. Results demonstrated that 3＇-methoxy-puerarin exhibited cerebroprotective effects against focal brain ischemia, which involved c-fos gene expression.

Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.

The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes

Background:In Type 1 diabetes,the insulin-producingβ-cells within the pancreatic islets of Langerhans are destroyed.We showed previously that immunotherapy with Bacillus Calmette-Guerin(BCG)or complete Freund’s adjuvant(CFA)of non-obese diabetic(NOD)mice can prevent disease process and pancreaticβ-cell loss.This was associated with increased islet Regenerating(Reg)genes expression,and elevated IL-22-producing Th17 T-cells in the pancreas.Results:We hypothesized that IL-22 was responsible for the increased Reg gene expression in the pancreas.We therefore quantified the Reg1,Reg2,and Reg3δ(INGAP)mRNA expression in isolated pre-diabetic NOD islets treated with IL-22.We measured IL-22,and IL-22 receptor(R)-αmRNA expression in the pancreas and spleen of pre-diabetic and diabetic NOD mice.Our results showed:1)Reg1 and Reg2 mRNA abundance to be significantly increased in IL-22-treated islets in vitro;2)IL-22 mRNA expression in the pre-diabetic mouse pancreas increased with time following CFA treatment;3)a reduced expression of IL-22Rαfollowing CFA treatment;4)a down-regulation in Reg1 and Reg2 mRNA expression in the pancreas of pre-diabetic mice injected with an IL-22 neutralizing antibody;and 5)an increased isletβ-cell DNA synthesis in vitro in the presence of IL-22.Conclusions:We conclude that IL-22 may contribute to the regeneration ofβ-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.

RegIV expression showing specificity to gastrointestinal tract and its potential role in diagnosing digestive tract neuroendocrine tumor

Regenerating gene IV （RegIV）, a member of the regenerating gene family discovered in 2001, has been found to be involved in malignancy in several different organs including the stomach, colorectum, pancreas and prostate, but the overall expression profile of RegIV has not been reported. To learn more about RegIV, we evaluated its distribution by immunohistochemistry （IHC） in a total of 360 samples including 24 types of normal tissue, 40 benign and malignant lesions, and 18 neuroendocrine tumors. We found that in normal tissues, in addition to its relative specificity for the gastrointestinal tract, RegIV was detected in the adrenal gland and mammary gland. Among all the malignancies of various histological types under evaluation, RegIV was found mostly in adenocarcinomas. Studies on additional sets of colorectal tumor samples showed that RegIV expression was predominant in colorectal adenoma （87.5%） and peritumoral tissue （100%） but not in cancer tissue （30.8%）. Among neuroendocrine tumors, ReglV had a relatively restricted expression to those of digestive system.