Cellular responses to carcinogens are typically studied in transformed cell lines, which do not reflect the physiological status of normal tissues. To address this question, we have characterized the transcriptional program and cellular responses of normal human lung WI-38 fibroblasts upon exposure to the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE). Exposure to BPDE induces a strong inflammatory response in WI-38 primary fibroblasts. Whole-genome microarray analysis shows induction of several genes related to the production of inflammatory factors, including those that encode interleukins (ILs), growth factors, and enzymes related to prostaglandin synthesis and signaling. This is the first demonstration that a strong inflammatory response is triggered in primary fibroblasts in response to a reactive diol epoxide derived from a polycyclic aromatic hydrocarbon.
Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway.
Specimen part
View SamplesThe molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the pre-ovulatory LH-surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal and granulosa cell type-specific biological functions and signaling pathways, large dominant bovine follicles were collected before and 21 hrs after an exogenous GnRH induced LH surge. Because LH receptor density varies within the granulosa cell populations, antral granulosa (aGC; those aspirated by follicular puncture) and membrane associated granulosa (mGC; those scraped from the follicular wall) were compared to thecal cell expression profiles determined by mRNA microarrays. Thecal cell gene expression was less affected in the peri-ovulatory follicle when compared to granulosa cells, as evidenced by only 2% versus 25% of the ~11,000 genes expressed changing in response to the LH surge, respectively. The majority of the 203 LH-regulated thecal genes were also LH regulated in granulosa cells, leaving a total of 58 genes as LH-regulated theca cell specific genes. Most of the 58 genes (i.e., 74%) thecal specific genes including several known thecal markers (CYP17A1, NR5A1) were downregulated, while most genes identified are new to theca. Many of the newly identified upregulated thecal genes (e.g., PTX3, RND3, PPP4R4) were also upregulated in granulosa. Minimal expression differences were observed between aGC and mGC, however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) predominated these differences. We also identified large numbers of unknown LH-regulated granulosa cell genes and discuss their putative roles in ovarian function.
Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.
Specimen part
View SamplesMating triggers physiological and behavioral changes in females.
Mating induces an immune response and developmental switch in the Drosophila oviduct.
No sample metadata fields
View SamplesHNF4alpha is a master regulator of hepatic differentiation. In this study, HNF4alpha was deleted in adult mice using a Cre-LoxP system where Cre recombinase was delivered using an AAV8 virus.
Hepatocyte-specific deletion of hepatocyte nuclear factor-4α in adult mice results in increased hepatocyte proliferation.
Age, Specimen part
View SamplesLiver undergoes both size increase and differentiation during postnatal period, which in mice is approximately first 30 days. The mechanisms of simultaneous postnatal liver cell proliferation and maturation are not clear. In these experiments, role of yes associated protein (Yap), the downstream effector of Hippo Kinase signaling pathway was investigated.
Yes-associated protein is involved in proliferation and differentiation during postnatal liver development.
Specimen part
View SamplesGold is widely considered to be a biologically inert element; however, it can elicit a profound biological response in plants. Plants can be exposed to significant levels of this precious metal in the environment from naturally occurring sources, as the result of mining activities or more recently resulting from the escalating use of nanoparticles in industry. In this microarray study we have investigated the gene expression response of Arabidopsis thaliana (Arabidopsis) to gold. Although the uptake of metal cations by plant transporters is well characterised, little is known about the uptake of gold, which exists in soil predominantly in a zero-valent state (Au0). We used this study to monitor the expression of candidate genes involved in metal uptake and transport. These show the down-regulation of a discreet number of genes known to be involved in the transport of copper, cadmium, nickel and iron.
Arabidopsis Glutathione Transferases U24 and U25 Exhibit a Range of Detoxification Activities with the Environmental Pollutant and Explosive, 2,4,6-Trinitrotoluene.
Specimen part, Treatment
View SamplesThe loss of REST in uterine fibroids promotes aberrant gene expression and enables mTOR pathway activation
Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway.
Specimen part, Treatment
View SamplesMouse mammary carcinoma cell line 4TO7 was used in this experiment. Six2 overepxression experiment.The mouse Six2 cDNA taken from CMV-sport6 (Open Biosystems) was cloned into a pcDNA3.1-hygromycin vector and transfected into 4TO7 cells, after which stably transfected cells were selected. Gene expression profiles were performed in triplicate for the control and over-expressed lines.
Homeoprotein Six2 promotes breast cancer metastasis via transcriptional and epigenetic control of E-cadherin expression.
Cell line
View SamplesImpact of mmu-miR-337-3p on the global gene expression in murine hepatoblasts.
MicroRNA-337-3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation.
Specimen part
View SamplesAutism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to decreased levels of brain BCAAs, abnormal mRNA translation and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function. Overall design: RNA-sequencing of cerebellum from 3 wildtype mice and 3 Slc7a5 KO mice
Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.
Specimen part, Subject
View Samples