Pathways that stimulate ß-cell regeneration remain of great clinical interest, yet effective therapeutic avenues that promote survival or reconstitution of ß-cell mass remain elusive. Utilizing a mouse model with inducible ß-cell apoptosis followed by adiponectin-mediated regeneration, we aimed to identify key molecules boosting ß-cell viability. Within the regenerating pancreatic islets, we examined changes within the transcriptome, and observed an extensive upregulation of genes encoding proteins involved in lipid transport and metabolism. The most prominent targets were further confirmed by quantitative PCR and immunofluorescence. Among the upstream regulators predicted by pathway analysis of the transcriptome, we detected enhanced levels of two key transcription factors, HNF4a and PPARa. Enhanced leptin levels in circulation may also contribute to the anti-lipotoxic program in islets. In summary, our data suggest that improving local lipid metabolism as an important anti-lipotoxic phenomenon to boost ß-cell regeneration, primarily mediated by adiponectin’s action on the ß-cells directly as well as on the adipocyte. Overall design: RNA profiles of pancreatic islets isolated from PANIC-ATTAT mice crossed with adiponectin wild-type (P-Adn+/+) or the overexpressing transgene (P-AdnTg/+) at 5 weeks after initial dimerizer administration.
Adiponectin-mediated antilipotoxic effects in regenerating pancreatic islets.
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View SamplesWe sorted for GFP+ cells using the enhancer trap J0571 with the UAS promoter driving the expression of different BIRD genes. Different genetic backgrounds are use and listed below.
Transcriptional control of tissue formation throughout root development.
Specimen part
View SamplesMetzincins and related genes (MARGS) play important roles in ECM remodeling in fibrotic conditions.
Renal Fibrosis mRNA Classifier: Validation in Experimental Lithium-Induced Interstitial Fibrosis in the Rat Kidney.
Sex, Specimen part
View SamplesRenal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Alteration of human blood cell transcriptome in uremia.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesAn assessment of a role of Ebf1 in committed B lineage cells.
Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells.
Specimen part
View SamplesTopical corticosteroids and calcineurin inhibitors are well known treatments of atopic dermatitis (AD), but differ in their efficacy and side effects. A study in AD patients has demonstrated that betamethasone valerate (BM) though clinically more efficient impaired skin barrier repair in contrast to pimecrolimus. Objective: The present study elucidates the mode of action of topical BM and pimecrolimus cream in AD.
Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Treatment
View SamplesGenome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Treatment
View SamplesGenome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Treatment
View SamplesIn a screen for upregulated adipocyte genes in insulin resistant versus insulin sensitive subjects matched for BMI, we identified the type II transmembrane protein tenomodulin (TNMD), previously implicated in glucose tolerance in gene association studies. TNMD expression was greatly increased in human preadipocytes during differentiation, while silencing TNMD blocked adipogenic gene induction and adipogenesis.
Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
Specimen part
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