Age-related frailty may in part be due to a decreased competency in skeletal muscle regeneration. The role of the closely related TGFbeta amily molecules myostatin and GDF11 in regeneration is unclear. The commercially available antibody which in a prior report was used to demonstrate an age-related decrease in GDF11 was found to detect both GDF11 and myostatin, and with this reagent it appears that the combination of GDF11 and myostatin increases with age in serum. Mechanistically, GDF11 and myostatin induce SMAD2/3 phosphorylation, and both inhibit myoblast differentiation and regulate identical downstream signaling. GDF11 injected into adult mice in a model of regeneration induces an increase in smaller fibers and a decrease in satellite cell expansion. There are no signs of benefit from GDF11 to regeneration. Thus, GDF11 appears to be an age-associated myokine that inhibits muscle differentiation, and is thus a target for blockade to treat frailty
GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.
Treatment, Time
View SamplesOur laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice
Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during ageing.
Sex
View SamplesTBX5 is hypomethylated in Rheumatoid Arthritis synovial fibroblasts (RASF). Hypomethylation increased the TBX5 expression in RASF.
Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts.
Specimen part
View SamplesMicroarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies.
New data on robustness of gene expression signatures in leukemia: comparison of three distinct total RNA preparation procedures.
No sample metadata fields
View SamplesIdentification of relevant subgroups in childhood MDS patients by gene expression analysis and gene involve in progression into AML
Gene expression signatures of pediatric myelodysplastic syndromes are associated with risk of evolution into acute myeloid leukemia.
Specimen part, Disease
View SamplesSummary:
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
No sample metadata fields
View SamplesProtein homeostasis in the endoplasmic reticulum (ER) has recently emerged as a therapeutic target for cancer treatment. Disruption of ER homeostasis results in ER stress, which is a major cause of cell death for cells exposed to the proteasome inhibitor Bortezomib, an anti-cancer drug approved for treatment of multiple myeloma and Mantle cell lymphoma. We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anti-cancer activities resembling that of Bortezomib.
The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group.
Cell line
View SamplesHEK293 cells were transfected with control plasmid (pcDNAI/Neo;Invitrogen) or with the plasmid encoding HCaRG. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen).
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
No sample metadata fields
View SamplesBackground: Diesel exhaust (DE) is the primary source of urban fine particulate matter, which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix platform (GeneChip Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 g/m of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes.
Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative analysis of resistant and susceptible macrophage gene expression response to Leishmania major parasite.
Specimen part
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