TGFbi (transforming growth factor-beta-induced) is a secreted protein and is capable of binding to both extracellular matrix (ECM) and cells. It thus acts as a bifunctional molecule enhancing ECM and cell interactions, a lack of which results in dysfunction of many cell types. In this study, we investigated the role of TGFbi in the function and survival of islets. Based on DNA microarray analysis followed by qPCR confirmation, the TGFbi gene showed drastic increases in expression in islets after culture. We demonstrated that recombinant TGFbi could preserve the integrity and enhance the function of cultured islets. Such a beneficial effect was mediated via signalling through FAK. Exogenous TGFbi was capable of sustaining high-level FAK phosphorylation in isolated islets, and FAK knockdown by siRNA in islets resulted in compromised islet function. TGFbi Tg islets showed better integrity and insulin release after in vitro culture. In vivo, b-cell proliferation was detectable in Tg but not wild type pancreata. At age above 12 months, Tg pancreata contained giant islets. Tg mice displayed better glucose tolerance than the controls. Tg islets were more potent in lowering blood glucose when transplanted into syngeneic mice with streptozotocin-induced diabetes, and these transplanted islets also underwent regeneration. Our results indicate that TGFbi is a vital trophic factor promoting islet survival, function and regeneration. At least some of its beneficial effect was mediated by signalling through FAK.
TGF-beta i promotes islet beta-cell function and regeneration.
Specimen part
View SamplesGene expression profiles of CD3e-proficient and CD3e-deficient were analysed using Affymetrix cDNA arrays (MOAE430)
Genetic interactions involved in TAL1- induced acute lymphoblastic leukemia
Age, Specimen part, Disease, Disease stage, Subject
View SamplesThe methyltransferase G9a was found to play a role in the disease progression of a murine model of AML.
The methyltransferase G9a regulates HoxA9-dependent transcription in AML.
Cell line
View SamplesThis study compared the photosynthetic performance and the global gene expression of the winter hardy wheat Triticum aestivum cv Norstar grown under non-acclimated (NA) or cold-acclimated (CA) condition at either ambient CO2 or elevated CO2 (EC). CA Norstar maintained comparable light saturated and CO2 saturated rates of photosynthesis but lower quantum requirements for photosystem II and non photochemical quenching relative to NA plants even at EC. Neither NA nor CA plants were sensitive to feedback inhibition of photosynthesis at EC. Global gene expression using microarray combined with bioinformatics analysis revealed that genes affected by EC were 3 times higher in NA (1022 genes) compared to CA (372 genes) Norstar. The most striking effect was the down-regulation of genes involved in the plant defense responses in NA Norstar. In contrast, cold acclimation reversed this down regulation due to the cold induction of genes involved in plant pathogenesis resistance, and cellular and chloroplast protection. These results suggest that EC have less impact on plant performance and productivity in cold adapted winter hardy plants in the northern climates compared to warmer environments. Selection for cereal cultivars with constitutively higher expression of biotic stress defense genes may be necessary under EC during the warm growth period and in warmer climates.
Long-term growth under elevated CO2 suppresses biotic stress genes in non-acclimated, but not cold-acclimated winter wheat.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesMyeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or polarization and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS).
MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.
Specimen part, Subject
View SamplesPrevious studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. In addition, we reported that C57Bl/6J mice did not form tumors under the same conditions.
Differential gene expression and methylation in the retinoid/PPARA pathway and of tumor suppressors may modify intestinal tumorigenesis induced by low folate in mice.
Sex, Specimen part, Treatment
View SamplesPrevious studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice.
Genes with aberrant expression in murine preneoplastic intestine show epigenetic and expression changes in normal mucosa of colon cancer patients.
Sex, Specimen part, Treatment
View SamplesPKR is an interferon induced serine/threonine protein kinase, that is activated by double stranded RNA. PKR plays an important role in the antiviral defense by interferon. In addition to its role in translation, PKR participates in several signaling pathways to transcription. The goal of this experiment is to study the role of PKR in regulating gene expression in our NIH 3T3 inducible cell line, which could overexpress PKR wt protein after the removal of tetracycline (Donze O, Dostie J, Sonenberg N. (1999) Virology 256: 322-9).
The protein kinase PKR: a molecular clock that sequentially activates survival and death programs.
Cell line
View Samples