Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA), a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury promoted significant recovery in locomotor function and marked an inhibition of TA noxious reflex activity (i.e., nociception) in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR. Comparison of the expression between healthy rats, SCI rats, and SCI treated with A-HOA rats revealed relevant changes in the expression of genes associated with neuronal morphogenesis and growth, neuronal survival, pain and inflammation. Thus, treatment with A-HOA not only induced a significant overexpression of growth and differentiation factor 10 (GDF10), tenascin C (TNC), aspirin (ASPN) and sushi-repeat-containing X-linked 2 (SRPX2), but also a significant reduction in the expression of prostaglandin E synthase (PTGES) and phospholipases A1 and A2 (PLA1/2). Currently, SCI has very important unmet clinical needs. A-HOA proved to downregulate genes involved in inflammation and upregulate genes involved in neuron growth, which balanced the important body response to medular lesion and allowed recovery from paralysis and pain.
Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation.
Specimen part
View SamplesThis study aims at a comprehensive understanding of the genomic program activated during early-phase of collateral vessel growth in a rat model for cerebral adaptive arteriogenesis (3-VO). While arteriogenesis constitutes a promising therapeutic concept for cerebrovascular ischemia, genomic profiles essential for therapeutic target identification were analysed solely for collateral arteries of the heart and periphery. Despite challenging anatomical conditions of the brain the 3-VO model allows identification of differentially expressed genes during adaptive cerebral arteriogenesis by selective removal of the posterior cerebral artery (PCA).
Induction of cerebral arteriogenesis leads to early-phase expression of protease inhibitors in growing collaterals of the brain.
Age
View SamplesAssay of gene expression pattern differences between liver cancer tissue and normal liver tissue from the same mouse by microarray in 4 separate mice injected with recombinant adeno-associated viral (AAV) vector
Assessing the potential for AAV vector genotoxicity in a murine model.
Sex, Specimen part
View SamplesAdministration of exogenous mesenchymal stem cells (MSCs) has been shown to improve the recovery from acute kidney injury (AKI). It has been suggested that the beneficial effect of MSCs is related to the paracrine release of factors favouring proliferation of intrinsic epithelial cells survived to injury rather than to their trans-differentiation. However the factors involved remain to be determined. In the present study we demonstrated that microvesicles (MVs) derived from human bone marrow MSCs are able to stimulate in vitro proliferation and apoptosis resistance of tubular epithelial cells (TEC). In addition, MVs were found to accelerate in vivo the morphological and functional recovery of glycerol induced AKI in SCID mice by inducing TEC proliferation. The effect of MVs on the recovery of AKI was comparable to that of human MSC treatment. In vitro we found that the CD44 and beta1-integrin-dependent incorporation of MVs in TEC was required for their biological action. However, despite their internalization, RNase-treated MVs failed to induce in vitro apoptosis resistance and TEC proliferation, and in vivo recovery from AKI, suggesting an RNA-dependent biological effect. Microarray analysis and quantitative RT-PCR of MV-RNA extract indicated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated with the mesenchymal differentiative phenotype and with several cell functions involved in the control of transcription, proliferation, apoptosis and cell immune regulation. These results suggest that MVs derived from MSCs may activate a proliferative program in TEC survived to injury in AKI by an horizontal transfer of mRNA.
Mesenchymal stem cell-derived microvesicles protect against acute tubular injury.
No sample metadata fields
View SamplesEpidermal stem cells ensure proper faring of skin homeostatic processes under both physiological and challenging conditions. Currently, the molecular events underpinning ageing within the epidermal stem cell niche are poorly understood.
In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells.
Age, Specimen part
View SamplesWe used whole-genome microarrays to identify differentially expressed genes in leaves of GA-deficient (35S::PcGA2ox) and/or GA-insensitive (35S::rgl1) transgenics as compared to WT poplar (717-1B4 genotype).
Roles of gibberellin catabolism and signaling in growth and physiological response to drought and short-day photoperiods in Populus trees.
Specimen part
View SamplesGene expression in LCLs from PA patients, their parents, and HapMap sex and age match controls at low glucose (9 mg/dL) and normal glucose growth conditions.
Gene expression in cell lines from propionic acidemia patients, carrier parents, and controls.
Sex, Age, Disease, Disease stage, Cell line, Treatment
View SamplesWe have used microarray technology to identify the transcriptional targets of Rho subfamily GTPases. This analysis indicated that murine fibroblasts transformed by these proteins show similar transcriptomal profiles. Functional annotation of the regulated genes indicate that Rho subfamily GTPases target a wide spectrum of biological functions, although loci encoding proteins linked to proliferation and DNA synthesis/transcription are up-regulated preferentially. Rho proteins promote four main networks of interacting proteins nucleated around E2F, c-Jun, c-Myc, and p53. Of those, E2F, c-Jun and c-Myc are essential for the maintenance of cell transformation. Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene expression without affecting the E2F and c-Jun pathways. Loss-of-function studies demonstrate that c-Myc is important for the blockage of cell-contact inhibition rather than for promoting the proliferation of Rho-transformed cells. However, c-Myc overexpression does not bypass the inhibition of cell transformation induced by Rock blockage, indicating that c-Myc is essential, but not sufficient, for Rock-dependent transformation. These results reveal the complexity of the genetic program orchestrated by the Rho subfamily and pinpoint protein networks that mediate different aspects of the malignant phenotype of Rho-transformed cells
Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases.
No sample metadata fields
View SamplesWe isolated the meristematic and elongation zones of Col-0, upb1-1 mutant and 35S::UPB1-3YFP/upb1-1 plants by micro-dissection and extracted RNA from each section independently.
Transcriptional regulation of ROS controls transition from proliferation to differentiation in the root.
Age, Specimen part
View SamplesTCP transcription factors from the CYC2-class are involved in the development of monosymmetric flowers in all core eudicot species analysed so far. In Antirrhinum majus, the CYC2/TCP transcription factor CYCLOIDEA (CYC) is the molecular key regulator driving the development of flower monosymmetry (Luo D, Carpenter R, Vincent C, Copsey L, Coen E: Origin of floral asymmetry in Antirrhinum. Nature 1996, 383:794-799). In the Brassicaceae Iberis amara, a stronger expression of the CYC2 gene IaTCP1 in the small adaxial petals likely leads to the reduced petal size in comparison to large abaxial petals, with hardly any IaTCP1 expression. This results in the formation of the monosymmetric Iberis flower (Busch A, Zachgo S: Control of corolla monosymmetry in the Brassicaceae Iberis amara. PNAS 2007, 104:16714-16719). In contrast, the orthologous TCP/CYC2 transcription factor TCP1 from Arabidopsis thaliana, which forms equally sized and shaped petal pairs, only shows an early and transient expression in the adaxial area of floral primordia. This implies that monosymmetry in the Brassicaceae evolved through a heterochronic expression shift of the TCP/CYC2 key regulator gene IaTCP1.
Differential transcriptome analysis reveals insight into monosymmetric corolla development of the crucifer Iberis amara.
Specimen part
View Samples