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GSE141905
Homo sapiens
12 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological processes involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts to an advanced 3D phenotypic high-content assay and screened a library of FDA/EMA approved small molecules for inhibiting ECM deposition. Fibrotic Pattern Detection by Artificial Intelligence (FANTAIL) identified Tranilast as an effective inhibitor, however, by structure-activity relationship studies we found N-(2-butoxyphenyl)-3-(phenyl)acrylamides (N23Ps) as a novel and highly potent compound class. N23Ps suppressed myofibroblast transdifferentiation, ECM deposition, cellular contractility, and altered cell shapes, thus advocating a unique mode of action. Mechanistically, transcriptomics identified SMAD (de)ubiquitination/Smurf2 as a potential therapeutic target network. Antifibrotic activity of N23Ps was verified by proteomics in a human ex vivo tissue fibrosis disease model, suppressing profibrotic markers SERPINE1/PAI1 and CXCL8/IL8. Conclusively, these data suggest N23Ps as a novel class of highly potent compounds with implications for inhibiting organ fibrosis in patients.
Publication Title
Phenotypic drug screening in a human fibrosis model identified a novel class of antifibrotic therapeutics.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Sca1+/cKit hematopoietic BMCs of hosts bearing instigating tumors (BPLER) promote the growth of responding (HMLER-HR) tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from mice bearing Non-instigating tumors lack this ability
Publication Title
Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the effects of recombinant granulin on human mammary stromal fibroblasts, we cultured normal human mammary fibroblasts in the presence of recombinant human granulin (1ug/ml) or PBS every 24h for 6 days.
Publication Title
Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The delicate interaction between cancer cells and the surrounding stroma plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer.
Publication Title
CD99 is a novel prognostic stromal marker in non-small cell lung cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BEAS-2B cells have been treated with low doses (20g/ml) of CSC for 4 months. As negative control BEAS-2B cells were treated with DMSO (the CSC solvent). Non-treated cells were cultivated in parallel.
Publication Title
Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study seeks to identify the epigenetic changes caused by exposure of to cigarette smoke condensate. To this goal human bronchial epithelial cells, BEAS-2B, were treated with 5-aza-2deoxycitidine and trychostatin A (5AzaC/TSA) subsequent to a chronic exposure (1 month) to cigarette smoke condensate (CSC). As negative control served BEAS-2B cells that were untreated or treated with CSC/DMSO for one month without the subsequent application of 5Aza/TSA.
Publication Title
Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Nitric oxide (NO) regulated pulmonary vascular function and structure, in part, via its effect on gene expression. We used microarrays to determine the up- and downregulated genes in rat pulmonary artery smooth muscle cells exposed to the NO donor S-nitrosoglutathione (GSNO) for 1, 2, and 4 hours.
Publication Title
Phosphodiesterase 3A expression is modulated by nitric oxide in rat pulmonary artery smooth muscle cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 91 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The aim was to analyze the transcriptome of different types of preneoplastic colorectal lesions in comparison with that of the corresponding normal mucosa.
Publication Title
Preinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid).
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Because it excises thymine from GT mismatches, TDG was proposed to counter mutagenesis by 5-methylcytosine deamination. Yet, TDG was also observed to attack 5-methycytosine itself, making it a candidate DNA demethylase, and interactions with transcription factors implicated additional functions in gene regulation. Unlike other DNA glycosylases, TDG is essential for embryonic development. Fibroblasts from Tdg null embryos show massively impaired gene regulation, and this correlates with imbalanced histone modification and CpG methylation. TDG associates with the promoters of affected genes in MEFs and in embryonic stem cells, but epigenetic aberrations appear only in differentiated cells. TDG also contributes to the maintenance of active and bivalent chromatin during cell differentiation, using its DNA glycosylase activity to counter aberrant de novo methylation. Thus, TDG dependent DNA repair stabilizes epigenetic states during cell differentiation.
Publication Title
Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability.
Sample Metadata Fields
Specimen part
View Samples